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    David Lambright PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-6876
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

        Overview 
        Narrative

        Academic Background

        David Lambright received his BS from the University of Lowell in 1984 and his PhD in chemistry from Stanford University in 1992. He was a Damon Runyon-Walter Winchell postdoctoral fellow from 1992-1995 in the Department of Molecular Biophysics and Biochemistry at Yale University. He joined the University of Massachusetts Medical School as a faculty member in the Program in Molecular Medicine in 1996. He is a recipient of a Scholar Award from the Leukemia & Lymphoma Society of America.

        Structural and molecular mechanisms of cell signaling and membrane trafficking

        Photo: David 
G. LambrightResearch in this laboratory is concerned with structural and molecular mechanisms of cell signaling and membrane trafficking. Our approach combines a broad range of experimental methods from diverse disciplines including biochemistry, biophysics, X-ray crystallography, and bioinformatics as well as molecular, cell, and systems biology. Areas of interest include the regulation of membrane trafficking by Rab GTPases, phosphoinositide signaling, and the regulation of cell proliferation. Defects in these fundamental regulatory mechanisms play critical roles in complex disease states such as cancer and diabetes as well as genetically linked disorders.

        Rab GTPases comprise a large family of molecular switches that function in membrane trafficking and organelle biogenesis by cycling between active (GTP bound) and inactive (GDP bound) states. Activation is regulated by guanine nucleotide exchange factors (GEFs), which promote exchange of GTP for GDP in response to extracellular or intracellular signals. Inactivation is regulated by GTPase-activating proteins (GAPs), which stimulate the hydrolysis of GTP. In the active state, Rab GTPases interact with a diverse effector proteins to regulate vesicle budding, cargo sorting, and motor-dependent transport as well as the tethering, docking, and fusion of vesicles with target membranes. We seek to understand the structural basis underlying the nucleotide dependent interactions of Rab GTPases with effectors and regulatory factors and determine the mechanisms by which these interactions regulate membrane trafficking. Towards this end, we have developed a novel structural proteomic strategy to profile interactions with the Rab family and determine the underlying structural bases. High throughput microplate assays are used to quantitatively profile interactions with GEFs, effectors, and GAPs. In addition to identifying novel interaction partners, the family-wide analyses facilitate crystallographic studies of Rab-GEF, Rab-effector, and Rab-GAP complexes and are also being used to characterize interactions of Rab GTPases with viral and bacterial virulence factors.

        Lipid second messengers known as phosphoinositides regulate a broad spectrum of cellular functions including survival, membrane trafficking, cytoskeletal dynamics, and migration. Targets of phosphoinositides include pleckstrin homology (PH) and FYVE domains in modular signaling and trafficking proteins. Our goal is to understand how phosphoinositide binding domains recognize phosphoinositides and elucidate the mechanisms by which phosphoinositides regulate the assembly and activation of multiprotein signaling and trafficking complexes on intracellular membranes.

        A third area of interest concerns an evolutionarily conserved protein, Zpr1, which is required for viability, normal cell cycle progression, and cell growth. Zpr1 is retained in the cytoplasm of quiescent cells through interactions with inactive growth factor receptors and, following stimulation, assembles into cytoplasmic complexes with elongation factor 1-alpha (eEF1A) and nuclear complexes with the survival motor neurons (SMN) protein. An exon deletion in the SMN1 gene that disrupts the interaction with Zpr1 is responsible for the most severe form of spinal muscular atrophy known as Werdnig-Hoffmann syndrome. We have solved the crystal structure of Zpr1 and are working on the structural bases underlying the interactions with growth factor receptors, EF1A, and the SMN complex.

        Figures

        GTPases and phosphoinositides

        Regulation of intracellular membrane trafficking

        The trafficking of lipids, integral membrane proteins and soluble cargo between membrane delimited organelles is regulated by GTPases of the Rab, Arf, Arl and Sar families as well as mono- and polyphosphorylated derivatives of phosphatidyl inositol (PIPs).

         

        Rabs Image  

         

         

        The Rab GTPase Cycle

        As evolutionarily conserved molecular switches, Rab GTPases cycle between inactive (GDP-bound) and active (GTP-bound) states.  In the active state, Rab GTPases interact with structurally and functionally diverse effectors including cargo sorting complexes on donor membranes, motor proteins involved in vesicular transport and tethering complexes that regulate vesicle fusion with acceptor membranes.  Rab GTPases are activated by guanine nucleotide exchange factors (GEFs) and deactivated by GTPase activating proteins (GAPs), which accelerate the slow intrinsic rates of nucleotide exchange and GTP hydrolysis.  Dual prenylation of C-terminal cysteine motifs allows Rab GTPases to partition with membranes.  Transfer between membranes is facilitated by GDP dissociation inhibitor (GDI) and GDI displacement factors (GDFs).  Targeting of Rab GTPases to specific organelles also depends on GEFs, effectors and GAPs.

         

        Rab Cycle Image  

         

        Membrane targeting mechanisms

        Lipid binding domains including those that recognize phosphoinositides utilize ligand-specific and/or non-specific mechanisms for partitioning with lipid bilayers.

         

        LBD Image  

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14679290&query_hl=1&itool=pubmed_docsum

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16807090&query_hl=1&itool=pubmed_docsum

         

        Rab family-wide interaction analyses

        Quantitative profiling of interactions with the Rab GTPase family

        Quantitative high throughput microplate assays are used to profile interactions of GEFs, GAPs and effectors with Rab GTPases.  Applications include determination of family-wide specificity profiles, identification of novel interaction partners and mutational analyses of specificity determinants.

         

        HTP Image  

        Activation of Rab GTPases by Vps9 domain GEFs

        Rab specificity profile for the Rabex-5 catalytic core

        Rab5 is an essential regulator of endosomal trafficking and endosome biogenesis.  Rabex-5 is a Rab5 GEF with a Vps9 domain homologous to the yeast Vps9 protein implicated in vacuolar protein sorting.  A profile of the Rab specificity of the catalytic core of Rabex-5 revealed equivalently high exchange activity for Rabs 5 and 21, weak activity for Rab22 and no detectable activity for 29 other Rab GTPases.  Rabs 5, 21 and 22 comprise a small phylogenetic subfamily of endosomal Rab GTPases.

         

        Rabex Profile Image  

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15339665&query_hl=1&itool=pubmed_docsum

         

        Rabex-5 structure and mutational analyses of recognition determinants

        The crystal structure of the Rabex-5 catalytic core revealed a tandem architecture consisting of a Vps9 domain stabilized by a helical bundle.  Conserved exchange determinants map to a common surface of the Vps9 domain, which recognizes invariant aromatic residues in the switch regions of Rab GTPases and selects for the Rab5 subfamily by requiring a small nonacidic residue preceding a critical phenylalanine in the switch I region.

        Rabex Structure Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15339665&query_hl=1&itool=pubmed_docsum

         

        Structural basis for Rab GTPase activation by Vps9 domain GEFs

        The crystal structure of the RABEX-5 helical bundle-Vps9 tandem in complex with nucleotide free RAB21 (a key intermediate in the exchange reaction pathway) revealed how the VPS9 domain recognizes Rab5 subfamily GTPases  (Rabs 5, 21 and 22), accelerates GDP release by destabilizing the magnesium binding site and subsequently stabilizes the high energy nucleotide free intermediate via an aspartic acid finger that simultaneously engages the P-loop lysine and switch II backbone.

         

        Rabex Rab21 Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17450153&query_hl=1&itool=pubmed_docsum

         

        Rab-effector recognition

        Structural genomic survey of the Rab family

        To understand how structural similarity and diversity in the active conformation of Rab GTPases contributes to effector recognition, we conducted a structural genomic survey of the mammalian Rab GTPase family.  The results revealed non-phylogenetic similarity and variability in the active conformations of Rab GTPases.

         

        SG Survey Image  

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

         

        Rab specificity profile of the multivalent effector Rabensoyn-5

        Surface plasmon resonance (SPR) was used to profile the interaction of the central and C-terminal Rab binding domains (RBDs) of the multivalent endosomal effector Rabenosyn-5 with the active form of 33 Rab GTPases.  Despite similar tertiary structures, the central and C-terminal RBDs recognize distinct subsets of Rab GTPases (Rabs 4 and 14 vs. Rabs 5, 22 and 24).

         

        Rbsn Profile Image  

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

         

        Structural basis for Rab GTPase recognition by Rabenosyn-5

        A truncation analysis of the multivalent Rab GTPase and PI3P effector Rabenosyn-5 mapped the central and C-terminal Rab binding domains (RBDs) to homologous regions.  Structures of the RBDs in complex with Rab4 and Rab22 revealed a common binding modality in which a structurally similar helical hairpin core in the RBDs engages a structurally similar active conformation of the switch and interswitch regions in the respective Rab GTPases.  Mutational analyses further revealed that the differential specificity of the RBDs is due in part to a non-conserved N-terminal extension (NTE) in RDB1 and in part to compositional differences within the conserved helical hairpin cores.

         

        r4r22rbsn Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

         

        Conceptual model for Rab-effector recognition

        The model shown here is based on known structures of Rab GTPases alone and in complex with effectors and takes into account the results of mutational analyses.  Structural variability influences the spatial disposition and exposure of the conserved residues, sub-dividing the Rab family into non-phylogenetic subsets that satisfy the structural requirements for effector recognition.  Compositional diversity within the switch/interswitch regions (and in certain cases CDRs) further refines the specificity through enhanced affinity for Rab GTPases with compatible compositions (positive selection) and/or reduced affinity for Rab GTPases with incompatible compositions (negative selection).  The family-wide nature of the recognition process is underscored by the conservation of positive determinants in interacting subsets and negative determinants in non-interacting Rab GTPases.  This model is also applicable to interactions with regulatory/accessory factors.

         

        RR Model Image

        Structural basis for recruitment of FIP3 to recycling endosomes

        Rab11 regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis.  A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognize the active form of Rab11.  Normal completion of cytokinesis requires a complex between Rab11 and FIP3.  Shown here is the structure of a heterotetrameric complex between constitutively active (GTP-bound) Rab11 and a FIP3 construct that includes the RBD.  Two Rab11 molecules bind to dyad symmetric sites at the C terminus of FIP3, which forms a non-canonical coiled-coiled dimer with a flared C terminus and hook region.  The RBD overlaps with the coiled coil and extends through the C-terminal hook.  Although FIP3 engages the switch and interswitch regions of Rab11, the mode of interaction differs from that of other Rab-effector complexes. In particular, the switch II region undergoes a large structural rearrangement that facilitates the interaction with FIP3.

         

        r11fip3 Image

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17007872&query_hl=1&itool=pubmed_docsum

         

        De-activation of Rab GTPases by TBC domain GAPs

        Rab specificity profile of the Gyp1p TBC domain GAP

        TBC (Tre-2, Bub2 and Cdc16) domains are broadly conserved in eukaryotes and function as GAPs for Rab GTPases as well as GTPases that control cytokinesis.  A profile of the specificity of the Gyp1p TBC domain revealed high GAP activity for Rab33 in addition to Rab1 (the mammalian homologue of the in vivo Gyp1p substrate Ypt1p).  The identification of Rab33 as a Gyp1p substrate facilitated determination of the structure of a TBC domain-Rab GTPase complex.

         

        gyp2 Profile Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16855591&query_hl=1&itool=pubmed_docsum

         

        TBC domains accelerate GTP hydrolysis by a dual finger mechanism     

        In the crystal structure of the Gyp1p TBC-domain-Rab33-aluminium fluoride complex, which approximates the transition-state intermediate for GTP hydrolysis, the TBC domain supplies two catalytic residues in trans, an arginine finger analogous to Ras/Rho family GAPs and a glutamine finger that substitutes for the glutamine in the DxxGQ motif of the GTPase.  The glutamine from the Rab GTPase does not stabilize the transition state as expected but instead interacts with the TBC domain.  Strong conservation of both catalytic fingers suggests that most TBC-domain GAPs will accelerate GTP hydrolysis by a similar dual-finger mechanism.  These conclusions are supported by mutational and complementation analyses.

         

        gyp1r33 Image  

                   

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16855591&query_hl=1&itool=pubmed_docsum

         

        Phosphoinositide recognition and membrane targeting

        Structural basis for 3-phosphoinositide recognition by PH domains

        The pleckstrin homology (PH) domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds PIP3 with high affinity.  The structure of the Grp1 PH domain bound to the head group of PIP3 (IP4) revealed a novel mode of phosphoinositide recognition involving a 20-residue beta hairpin insertion within the beta6/beta7 loop.   The observed mode of recognition involving residues from a conserved basic motif as well as the variable loops surrounding the phosphoinositide binding site explains the high affinity and specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains that lack the hairpin insertion.

         

        grp1 Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10983985&query_hl=1&itool=pubmed_DocSum

         

        Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains

        The PH domains of the homologous proteins Grp1, ARNO and Cytohesin-1 bind PIP3 with unusually high selectivity.  Remarkably, splice variants that differ only by the insertion of a single glycine residue in the beta1/beta2 loop exhibit dual specificity for PIP2 and PIP3.  Crystal structures for the dual specificity 'triglycine' variant of the ARNO PH domain in complex with the head groups of PIP2 (IP3) and PIP3 (IP4) revealed the structural basis underlying this dramatic selectivity switch.  Loss of contacts with the beta1/beta2 loop with no significant change in head group orientation accounts for the significant decrease in PIP3 affinity observed for the dual specificity variants.  Conversely, a small increase rather than decrease in affinity for PIP2 is explained by a novel 'rotated' binding mode, in which the glycine insertion alleviates unfavorable interactions with the beta1/beta2 loop. These and other observations supported by systematic mutational analyses suggested a general model for phosphoinositide recognition by PH domains that conserve a 'signature' basic motif.

         

        arno Image  

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15359279&query_hl=1&itool=pubmed_docsum

         

        Structural basis for PI3P recognition and multivalent endosome targeting by FYVE domains

        The localization of the early endosomal marker and tethering factor EEA1 is mediated by a C-terminal region that includes a calmodulin binding motif, a Rab5 binding site and a FYVE domain that selectively binds PI3P.  The crystal structure of the C-terminal region bound to the head group of PI3P (IP2) revealed an organized quaternary assembly consisting of a parallel coiled coil and a dyad-symmetric FYVE domain homodimer. Structural and biochemical observations support a multivalent mechanism for endosomal targeting in which domain organization, dimerization and quaternary structure amplify the weak affinity and modest specificity of head group interactions with conserved residues.

         

        eea1 Image 

         

        For additional information, see:

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11741531&query_hl=1&itool=pubmed_docsum

         



        Rotation Projects

        Lab Rotations

        Our lab takes an interdisciplinary approach to the study of fundamental problems in cell biology, signal transduction and membrane trafficking. Rotation projects are available in any of the areas of interest to the lab. Projects are tailored to the individual interests of the students and often involve a combination of molecular, biochemical, biophysical, structural and/or cell based analyses to investigate signaling and trafficking mechanisms.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Lambright for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Hubber A, Arasaki K, Nakatsu F, Hardiman C, Lambright D, De Camilli P, Nagai H, Roy CR. The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple legionella effector proteins. PLoS Pathog. 2014 Jul; 10(7):e1004222.
          View in: PubMed
        2. Del Campo CM, Mishra AK, Wang YH, Roy CR, Janmey PA, Lambright DG. Structural Basis for PI(4)P-Specific Membrane Recruitment of the Legionella pneumophila Effector DrrA/SidM. Structure. 2014 Mar 4; 22(3):397-408.
          View in: PubMed
        3. Malaby AW, van den Berg B, Lambright DG. Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors. Proc Natl Acad Sci U S A. 2013 Aug 27; 110(35):14213-8.
          View in: PubMed
        4. Mishra AK, Del Campo CM, Collins RE, Roy CR, Lambright DG. The Legionella pneumophila GTPase activating protein LepB accelerates Rab1 deactivation by a non-canonical hydrolytic mechanism. J Biol Chem. 2013 Aug 16; 288(33):24000-11.
          View in: PubMed
        5. Mannstadt M, Harris M, Bravenboer B, Chitturi S, Dreijerink KM, Lambright DG, Lim ET, Daly MJ, Gabriel S, Jüppner H. Germline mutations affecting Ga11 in hypoparathyroidism. N Engl J Med. 2013 Jun 27; 368(26):2532-4.
          View in: PubMed
        6. Tan SX, Ng Y, Burchfield JG, Ramm G, Lambright DG, Stöckli J, James DE. The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes. Mol Cell Biol. 2012 Dec; 32(24):4946-59.
          View in: PubMed
        7. Davey JR, Humphrey SJ, Junutula JR, Mishra AK, Lambright DG, James DE, Stöckli J. TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes. Traffic. 2012 Oct; 13(10):1429-41.
          View in: PubMed
        8. Nottingham RM, Pusapati GV, Ganley IG, Barr FA, Lambright DG, Pfeffer SR. RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36. J Biol Chem. 2012 Jun 29; 287(27):22740-8.
          View in: PubMed
        9. Li J, Malaby AW, Famulok M, Sabe H, Lambright DG, Hsu VW. Grp1 plays a key role in linking insulin signaling to glut4 recycling. Dev Cell. 2012 Jun 12; 22(6):1286-98.
          View in: PubMed
        10. Navaroli DM, Bellvé KD, Standley C, Lifshitz LM, Cardia J, Lambright D, Leonard D, Fogarty KE, Corvera S. Rabenosyn-5 defines the fate of the transferrin receptor following clathrin-mediated endocytosis. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):E471-80.
          View in: PubMed
        11. Nottingham RM, Ganley IG, Barr FA, Lambright DG, Pfeffer SR. RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. J Biol Chem. 2011 Sep 23; 286(38):33213-22.
          View in: PubMed
        12. DiNitto JP, Lee MT, Malaby AW, Lambright DG. Specificity and membrane partitioning of Grsp1 signaling complexes with Grp1 family Arf exchange factors. Biochemistry. 2010 Jul 27; 49(29):6083-92.
          View in: PubMed
        13. Zhou QL, Jiang ZY, Mabardy AS, Del Campo CM, Lambright DG, Holik J, Fogarty KE, Straubhaar J, Nicoloro S, Chawla A, Czech MP. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem. 2010 Sep 3; 285(36):27581-9.
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        14. Mishra A, Eathiraj S, Corvera S, Lambright DG. Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proc Natl Acad Sci U S A. 2010 Jun 15; 107(24):10866-71.
          View in: PubMed
        15. Chotard L, Mishra AK, Sylvain MA, Tuck S, Lambright DG, Rocheleau CE. TBC-2 regulates RAB-5/RAB-7-mediated endosomal trafficking in Caenorhabditis elegans. Mol Biol Cell. 2010 Jul 1; 21(13):2285-96.
          View in: PubMed
        16. Barr F, Lambright DG. Rab GEFs and GAPs. Curr Opin Cell Biol. 2010 Aug; 22(4):461-70.
          View in: PubMed
        17. Fang Z, Takizawa N, Wilson KA, Smith TC, Delprato A, Davidson MW, Lambright DG, Luna EJ. The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility. Traffic. 2010 Jun; 11(6):782-99.
          View in: PubMed
        18. Lee MT, Mishra A, Lambright DG. Structural mechanisms for regulation of membrane traffic by rab GTPases. Traffic. 2009 Oct; 10(10):1377-89.
          View in: PubMed
        19. Leonard D, Hayakawa A, Lawe D, Lambright D, Bellve KD, Standley C, Lifshitz LM, Fogarty KE, Corvera S. Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes. J Cell Sci. 2008 Oct 15; 121(Pt 20):3445-58.
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        20. DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG. Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors. Mol Cell. 2007 Nov 30; 28(4):569-83.
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        21. Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature. 2007 Nov 15; 450(7168):365-9.
          View in: PubMed
        22. Sklan EH, Serrano RL, Einav S, Pfeffer SR, Lambright DG, Glenn JS. TBC1D20 is a Rab1 GTPase-activating protein that mediates hepatitis C virus replication. J Biol Chem. 2007 Dec 14; 282(50):36354-61.
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        23. Mukhopadhyay A, Pan X, Lambright DG, Tissenbaum HA. An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Rep. 2007 Oct; 8(10):931-8.
          View in: PubMed
        24. Mishra AK, Gangwani L, Davis RJ, Lambright DG. Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Proc Natl Acad Sci U S A. 2007 Aug 28; 104(35):13930-5.
          View in: PubMed
        25. Delprato A, Lambright DG. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat Struct Mol Biol. 2007 May; 14(5):406-12.
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        26. Hayakawa A, Hayes S, Leonard D, Lambright D, Corvera S. Evolutionarily conserved structural and functional roles of the FYVE domain. Biochem Soc Symp. 2007; (74):95-105.
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        27. Eathiraj S, Mishra A, Prekeris R, Lambright DG. Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes. J Mol Biol. 2006 Nov 24; 364(2):121-35.
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        28. Morrison AR, Moss J, Stevens LA, Evans JE, Farrell C, Merithew E, Lambright DG, Greiner DL, Mordes JP, Rossini AA, Bortell R. ART2, a T cell surface mono-ADP-ribosyltransferase, generates extracellular poly(ADP-ribose). J Biol Chem. 2006 Nov 3; 281(44):33363-72.
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        29. Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat Cell Biol. 2006 Sep; 8(9):971-7.
          View in: PubMed
        30. Hayakawa A, Leonard D, Murphy S, Hayes S, Soto M, Fogarty K, Standley C, Bellve K, Lambright D, Mello C, Corvera S. The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis. Proc Natl Acad Sci U S A. 2006 Aug 8; 103(32):11928-33.
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        31. Pan X, Eathiraj S, Munson M, Lambright DG. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature. 2006 Jul 20; 442(7100):303-6.
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        32. DiNitto JP, Lambright DG. Membrane and juxtamembrane targeting by PH and PTB domains. Biochim Biophys Acta. 2006 Aug; 1761(8):850-67.
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        33. Eathiraj S, Lambright DG. ESCRT complexes assembled and GLUEd. Structure. 2006 Apr; 14(4):631-2.
          View in: PubMed
        34. Eathiraj S, Pan X, Ritacco C, Lambright DG. Structural basis of family-wide Rab GTPase recognition by rabenosyn-5. Nature. 2005 Jul 21; 436(7049):415-9.
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        35. Cronin TC, DiNitto JP, Czech MP, Lambright DG. Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains. EMBO J. 2004 Oct 1; 23(19):3711-20.
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        36. Delprato A, Merithew E, Lambright DG. Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5. Cell. 2004 Sep 3; 118(5):607-17.
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        37. DiNitto JP, Cronin TC, Lambright DG. Membrane recognition and targeting by lipid-binding domains. Sci STKE. 2003 Dec 16; 2003(213):re16.
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        38. Hayakawa A, Hayes SJ, Lawe DC, Sudharshan E, Tuft R, Fogarty K, Lambright D, Corvera S. Structural basis for endosomal targeting by FYVE domains. J Biol Chem. 2004 Feb 13; 279(7):5958-66.
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        39. Lawe DC, Sitouah N, Hayes S, Chawla A, Virbasius JV, Tuft R, Fogarty K, Lifshitz L, Lambright D, Corvera S. Essential role of Ca2+/calmodulin in Early Endosome Antigen-1 localization. Mol Biol Cell. 2003 Jul; 14(7):2935-45.
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        40. Merithew E, Stone C, Eathiraj S, Lambright DG. Determinants of Rab5 interaction with the N terminus of early endosome antigen 1. J Biol Chem. 2003 Mar 7; 278(10):8494-500.
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        41. Weston CR, Lambright DG, Davis RJ. Signal transduction. MAP kinase signaling specificity. Science. 2002 Jun 28; 296(5577):2345-7.
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        42. Merithew E, Lambright DG. Calculating the potential of C2 domains for membrane binding. Dev Cell. 2002 Feb; 2(2):132-3.
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        43. Zhu Z, Delprato A, Merithew E, Lambright DG. Determinants of the broad recognition of exocytic Rab GTPases by Mss4. Biochemistry. 2001 Dec 25; 40(51):15699-706.
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        44. Dumas JJ, Merithew E, Sudharshan E, Rajamani D, Hayes S, Lawe D, Corvera S, Lambright DG. Multivalent endosome targeting by homodimeric EEA1. Mol Cell. 2001 Nov; 8(5):947-58.
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        45. Lawe DC, Chawla A, Merithew E, Dumas J, Carrington W, Fogarty K, Lifshitz L, Tuft R, Lambright D, Corvera S. Sequential roles for phosphatidylinositol 3-phosphate and Rab5 in tethering and fusion of early endosomes via their interaction with EEA1. J Biol Chem. 2002 Mar 8; 277(10):8611-7.
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        46. Zhu Z, Dumas JJ, Lietzke SE, Lambright DG. A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release. Biochemistry. 2001 Mar 13; 40(10):3027-36.
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        47. Merithew E, Hatherly S, Dumas JJ, Lawe DC, Heller-Harrison R, Lambright DG. Structural plasticity of an invariant hydrophobic triad in the switch regions of Rab GTPases is a determinant of effector recognition. J Biol Chem. 2001 Apr 27; 276(17):13982-8.
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        48. Lietzke SE, Bose S, Cronin T, Klarlund J, Chawla A, Czech MP, Lambright DG. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol Cell. 2000 Aug; 6(2):385-94.
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        49. Lawe DC, Patki V, Heller-Harrison R, Lambright D, Corvera S. The FYVE domain of early endosome antigen 1 is required for both phosphatidylinositol 3-phosphate and Rab5 binding. Critical role of this dual interaction for endosomal localization. J Biol Chem. 2000 Feb 4; 275(5):3699-705.
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        50. Dumas JJ, Zhu Z, Connolly JL, Lambright DG. Structural basis of activation and GTP hydrolysis in Rab proteins. Structure. 1999 Apr 15; 7(4):413-23.
          View in: PubMed
        51. Dumas JJ, Lambright DG. Gs alpha meets its target--shedding light on a key signal transduction event. Structure. 1998 Apr 15; 6(4):407-11.
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        52. Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature. 1996 Jan 25; 379(6563):311-9.
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        53. Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature. 1996 Jan 25; 379(6563):369-74.
          View in: PubMed
        54. Sondek J, Lambright DG, Noel JP, Hamm HE, Sigler PB. GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature. 1994 Nov 17; 372(6503):276-9.
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        55. Balasubramanian S, Lambright DG, Simmons JH, Gill SJ, Boxer SG. Determination of the carbon monoxide binding constants of myoglobin mutants: comparison of kinetic and equilibrium methods. Biochemistry. 1994 Jul 12; 33(27):8355-60.
          View in: PubMed
        56. Lambright DG, Noel JP, Hamm HE, Sigler PB. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature. 1994 Jun 23; 369(6482):621-8.
          View in: PubMed
        57. Lambright DG, Balasubramanian S, Decatur SM, Boxer SG. Anatomy and dynamics of a ligand-binding pathway in myoglobin: the roles of residues 45, 60, 64, and 68. Biochemistry. 1994 May 10; 33(18):5518-25.
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        58. Petrich JW, Lambry JC, Balasubramanian S, Lambright DG, Boxer SG, Martin JL. Ultrafast measurements of geminate recombination of NO with site-specific mutants of human myoglobin. J Mol Biol. 1994 May 6; 238(3):437-44.
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        59. Lambright DG, Balasubramanian S, Boxer SG. Dynamics of protein relaxation in site-specific mutants of human myoglobin. Biochemistry. 1993 Sep 28; 32(38):10116-24.
          View in: PubMed
        60. Balasubramanian S, Lambright DG, Marden MC, Boxer SG. CO recombination to human myoglobin mutants in glycerol-water solutions. Biochemistry. 1993 Mar 9; 32(9):2202-12.
          View in: PubMed
        61. Hubbard SR, Hendrickson WA, Lambright DG, Boxer SG. X-ray crystal structure of a recombinant human myoglobin mutant at 2.8 A resolution. J Mol Biol. 1990 May 20; 213(2):215-8.
          View in: PubMed
        62. Lambright DG, Balasubramanian S, Boxer SG. Ligand and proton exchange dynamics in recombinant human myoglobin mutants. J Mol Biol. 1989 May 5; 207(1):289-99.
          View in: PubMed
        63. Varadarajan R, Lambright DG, Boxer SG. Electrostatic interactions in wild-type and mutant recombinant human myoglobins. Biochemistry. 1989 May 2; 28(9):3771-81.
          View in: PubMed
        64. Johnson DR, Lambright DG, Wong SS. Lactose synthase: effect of alpha-lactalbumin on substrate activity of N-acylglucosamines. Biochim Biophys Acta. 1985 Dec 20; 832(3):373-7.
          View in: PubMed
        65. Lambright DG, Lee TK, Wong SS. Association-dissociation modulation of enzyme activity: case of lactose synthase. Biochemistry. 1985 Feb 12; 24(4):910-4.
          View in: PubMed
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