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James Reid Gilmore PhD

TitleProfessor Emeritus
InstitutionUMass Chan Medical School
DepartmentBiochemistry and Molecular Biotechnology
AddressUMass Chan Medical School
364 Plantation Street LRB
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    Collapse Biography 
    Collapse education and training
    University of New Mexico Albuquerque, Albuquerque, NM, United StatesBSChemistry
    University of Illinois, Urbana-Champaign, Champaign, IL, United StatesMSBiochemistry
    University of Illinois, Urbana-Champaign, Champaign, IL, United StatesPHDBiochemistry

    Collapse Overview 
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    PhD, University of Illinois, Urbana, 1980
    Postdoctoral Training
    The Rockefeller University, 1980-1983

    Molecular mechanism of secretory protein translocation

    Reid Gilmore

    The objective of research in our laboratory is to understand how proteins reach their final destinations within a cell. Specifically, we are investigating the biosynthesis, translocation, processing and folding of proteins in the rough endoplasmic reticulum.

    A major goal of our lab is to elucidate the mechanism of protein translocation across the rough endoplasmic reticulum (RER) membrane. The signal recognition particle (SRP), a ribonucleoprotein that binds to the polypeptide exit site on the ribosome, and the membrane bound SRP receptor (SR) function together to selectively attach a ribosome synthesizing a protein with an RER signal sequences to the Sec61 complex. The Sec61 heterotrimer forms an evolutionarily conserved channel for translocation of secreted proteins and integration of membrane proteins. We are using the Saccharomyces cerevisiae experimental to analyze the mechanism of translocation channel gating by ribosome-nascent chain complexes. Novel Sec61 mutants are designed based upon the structure of the Methanococcus janaschii SecYEb complex. The in vivo kinetics of protein translocation channel gating are being analyzed using ubiquitin translocation assay (UTA) reporters.

    Asparagine-linked glycosylation of proteins occurs within the lumen of the RER. Oligosaccharyltransferase (OST) catalyzes the transfer of a preassembled high-mannose oligosaccharide onto N-X-T or N-X-S acceptor sites (seqons) as the nascent polypeptide is transported into the RER lumen through the Sec61 complex. The oligosaccharide donor for the enzyme is the dolichol pyrophosphate linked oligosaccharide GlcNAc2Man9Glc3. The oligosaccharyltransferase is a hetero-octameric integral membrane protein in higher eukaryotes. Many unicellular protists have simpler OSTs with either a single subunit (e.g. Trypanosoma cruzi) or four subunits (e.g. Entamoeba histolytica). The active site subunit of the OST is the STT3 protein. Interestingly, the genomes of insects, plants and vertebrates encode two STT3 proteins. Biochemical experiments have revealed that the two SST3 proteins (STT3A and STT3B) assemble with a shared set of non-catalytic subunits into two separate OST complexes with different kinetic properties. We are analyzing the roles of these two distinct OST complexes in tissue culture cells by selectively knocking down STT3A or STT3B expression using siRNAs. Current evidence indicates that the STT3A isoform of the OST is primarily responsible for cotranslational glycosylation of nascent glycoproteins as the acceptor sequons exit the luminal face of the translocation channel. The STT3B isoform of the OST can modify skipped sequons on unfolded proteins in the lumen of the ER.

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    Rotation Project Background

    In yeast cells, protein translocation across the endoplasmic reticulum can occur by cotranslational or posttranslational pathways.  The objective of this project is to develop a rapid method to inactivate the posttranslational pathway in vivo in yeast cells by appending the CMV-ribosome stalling sequence to the C-terminus of a typical posttranslational translocation substrate (carboxypeptidase Y).  Complexes between the posttranslational translocation channel (SEC complex) and the stalled ribosomes will be purified for structural and functional analysis.  

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Cherepanova NA, Venev SV, Leszyk JD, Shaffer SA, Gilmore R. Quantitative glycoproteomics reveals new classes of STT3A- and STT3B-dependent N-glycosylation sites. J Cell Biol. 2019 08 05; 218(8):2782-2796. PMID: 31296534.
      Citations: 28     Fields:    Translation:HumansCells
    2. Klaver E, Zhao P, May M, Flanagan-Steet H, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R. Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing. Dis Model Mech. 2019 06 05; 12(6). PMID: 31101650.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    3. Blommaert E, P?anne R, Cherepanova NA, Rymen D, Staels F, Jaeken J, Race V, Keldermans L, Souche E, Corveleyn A, Sparkes R, Bhattacharya K, Devalck C, Schrijvers R, Foulquier F, Gilmore R, Matthijs G. Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype. Proc Natl Acad Sci U S A. 2019 05 14; 116(20):9865-9870. PMID: 31036665.
      Citations: 37     Fields:    Translation:Humans
    4. Shrimal S, Gilmore R. Oligosaccharyltransferase structures provide novel insight into the mechanism of asparagine-linked glycosylation in prokaryotic and eukaryotic cells. Glycobiology. 2019 04 01; 29(4):288-297. PMID: 30312397.
      Citations: 21     Fields:    Translation:HumansCells
    5. Lu H, Cherepanova NA, Gilmore R, Contessa JN, Lehrman MA. Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction. FASEB J. 2019 06; 33(6):6801-6812. PMID: 30811219.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    6. Chang IJ, Byers HM, Ng BG, Merritt JL, Gilmore R, Shrimal S, Wei W, Zhang Y, Blair AB, Freeze HH, Zhang B, Lam C. Factor VIII and vWF deficiency in STT3A-CDG. J Inherit Metab Dis. 2019 03; 42(2):325-332. PMID: 30701557.
      Citations: 4     Fields:    Translation:HumansCells
    7. Lu H, Fermaintt CS, Cherepanova NA, Gilmore R, Yan N, Lehrman MA. Mammalian STT3A/B oligosaccharyltransferases segregate N-glycosylation at the translocon from lipid-linked oligosaccharide hydrolysis. Proc Natl Acad Sci U S A. 2018 09 18; 115(38):9557-9562. PMID: 30181269.
      Citations: 12     Fields:    Translation:HumansAnimalsCells
    8. Rinis N, Golden JE, Marceau CD, Carette JE, Van Zandt MC, Gilmore R, Contessa JN. Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors. Cell Chem Biol. 2018 10 18; 25(10):1231-1241.e4. PMID: 30078634.
      Citations: 23     Fields:    Translation:HumansCells
    9. Mandon EC, Butova C, Lachapelle A, Gilmore R. Conserved motifs on the cytoplasmic face of the protein translocation channel are critical for the transition between resting and active conformations. J Biol Chem. 2018 08 31; 293(35):13662-13672. PMID: 29986881.
      Citations: 4     Fields:    Translation:AnimalsCells
    10. Braunger K, Pfeffer S, Shrimal S, Gilmore R, Berninghausen O, Mandon EC, Becker T, F?rster F, Beckmann R. Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum. Science. 2018 04 13; 360(6385):215-219. PMID: 29519914.
      Citations: 88     Fields:    Translation:HumansCells
    11. Wei W, Misra S, Cannon MV, Yang R, Zhu X, Gilmore R, Zhu M, Zhang B. Molecular mechanisms of missense mutations that generate ectopic N-glycosylation sites in coagulation factor VIII. Biochem J. 2018 03 06; 475(5):873-886. PMID: 29444815.
      Citations: 6     Fields:    Translation:HumansCells
    12. Shrimal S, Cherepanova NA, Gilmore R. One flexible loop in OST lassos both substrates. Nat Struct Mol Biol. 2017 12 07; 24(12):1009-1010. PMID: 29215637.
      Citations: 3     Fields:    Translation:Cells
    13. Shrimal S, Cherepanova NA, Gilmore R. DC2 and KCP2 mediate the interaction between the oligosaccharyltransferase and the ER translocon. J Cell Biol. 2017 11 06; 216(11):3625-3638. PMID: 28860277.
      Citations: 23     Fields:    Translation:HumansCells
    14. Lin DL, Cherepanova NA, Bozzacco L, MacDonald MR, Gilmore R, Tai AW. Dengue Virus Hijacks a Noncanonical Oxidoreductase Function of a Cellular Oligosaccharyltransferase Complex. mBio. 2017 07 18; 8(4). PMID: 28720733.
      Citations: 38     Fields:    Translation:HumansCells
    15. Tripathi A, Mandon EC, Gilmore R, Rapoport TA. Two alternative binding mechanisms connect the protein translocation Sec71-Sec72 complex with heat shock proteins. J Biol Chem. 2017 05 12; 292(19):8007-8018. PMID: 28286332.
      Citations: 22     Fields:    Translation:AnimalsCells
    16. Lopez-Sambrooks C, Shrimal S, Khodier C, Flaherty DP, Rinis N, Charest JC, Gao N, Zhao P, Wells L, Lewis TA, Lehrman MA, Gilmore R, Golden JE, Contessa JN. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. Nat Chem Biol. 2016 Dec; 12(12):1023-1030. PMID: 27694802.
      Citations: 48     Fields:    Translation:HumansCells
    17. Cherepanova N, Shrimal S, Gilmore R. N-linked glycosylation and homeostasis of the endoplasmic reticulum. Curr Opin Cell Biol. 2016 08; 41:57-65. PMID: 27085638.
      Citations: 91     Fields:    Translation:HumansAnimalsCells
    18. Cherepanova NA, Gilmore R. Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. Sci Rep. 2016 Feb 11; 6:20946. PMID: 26864433.
      Citations: 47     Fields:    Translation:HumansAnimalsCells
    19. Shrimal S, Gilmore R. Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor. Glycobiology. 2015 Jul; 25(7):774-83. PMID: 25792706.
      Citations: 10     Fields:    Translation:HumansCells
    20. Shrimal S, Cherepanova NA, Gilmore R. Cotranslational and posttranslocational N-glycosylation of proteins in the endoplasmic reticulum. Semin Cell Dev Biol. 2015 May; 41:71-8. PMID: 25460543.
      Citations: 63     Fields:    Translation:HumansAnimalsCells
    21. Cherepanova NA, Shrimal S, Gilmore R. Oxidoreductase activity is necessary for N-glycosylation of cysteine-proximal acceptor sites in glycoproteins. J Cell Biol. 2014 Aug 18; 206(4):525-39. PMID: 25135935.
      Citations: 52     Fields:    Translation:HumansCells
    22. Shrimal S, Gilmore R. Glycosylation of closely spaced acceptor sites in human glycoproteins. J Cell Sci. 2013 Dec 01; 126(Pt 23):5513-23. PMID: 24105266.
      Citations: 32     Fields:    Translation:HumansAnimalsCells
    23. Shrimal S, Ng BG, Losfeld ME, Gilmore R, Freeze HH. Mutations in STT3A and STT3B cause two congenital disorders of glycosylation. Hum Mol Genet. 2013 Nov 15; 22(22):4638-45. PMID: 23842455.
      Citations: 39     Fields:    Translation:HumansCells
    24. Shrimal S, Trueman SF, Gilmore R. Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST. J Cell Biol. 2013 Apr 01; 201(1):81-95. PMID: 23530066.
      Citations: 55     Fields:    Translation:HumansCells
    25. Mandon EC, Trueman SF, Gilmore R. Protein translocation across the rough endoplasmic reticulum. Cold Spring Harb Perspect Biol. 2013 Feb 01; 5(2). PMID: 23251026.
      Citations: 32     Fields:    Translation:Cells
    26. Trueman SF, Mandon EC, Gilmore R. A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function. J Cell Biol. 2012 Dec 10; 199(6):907-18. PMID: 23229898.
      Citations: 35     Fields:    Translation:AnimalsCells
    27. Gilmore R, Mandon EC. Understanding integration of a-helical membrane proteins: the next steps. Trends Biochem Sci. 2012 Aug; 37(8):303-8. PMID: 22748693.
      Citations: 2     Fields:    Translation:AnimalsCells
    28. Zhang X, Garbett K, Veeraraghavalu K, Wilburn B, Gilmore R, Mirnics K, Sisodia SS. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. J Neurosci. 2012 Jun 20; 32(25):8633-48. PMID: 22723704.
      Citations: 66     Fields:    Translation:HumansAnimalsCells
    29. Trueman SF, Mandon EC, Gilmore R. Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity. Mol Biol Cell. 2011 Sep; 22(17):2983-93. PMID: 21737680.
      Citations: 21     Fields:    Translation:AnimalsCells
    30. Gilmore R. Structural biology: Porthole to catalysis. Nature. 2011 Jun 15; 474(7351):292-3. PMID: 21677742.
      Citations: 2     Fields:    Translation:Cells
    31. Bas T, Gao GY, Lvov A, Chandrasekhar KD, Gilmore R, Kobertz WR. Post-translational N-glycosylation of type I transmembrane KCNE1 peptides: implications for membrane protein biogenesis and disease. J Biol Chem. 2011 Aug 12; 286(32):28150-9. PMID: 21676880.
      Citations: 21     Fields:    Translation:HumansAnimalsCells
    32. Becker T, Bhushan S, Jarasch A, Armache JP, Funes S, Jossinet F, Gumbart J, Mielke T, Berninghausen O, Schulten K, Westhof E, Gilmore R, Mandon EC, Beckmann R. Structure of monomeric yeast and mammalian Sec61 complexes interacting with the translating ribosome. Science. 2009 Dec 04; 326(5958):1369-73. PMID: 19933108.
      Citations: 145     Fields:    Translation:AnimalsCells
    33. Mandon EC, Trueman SF, Gilmore R. Translocation of proteins through the Sec61 and SecYEG channels. Curr Opin Cell Biol. 2009 Aug; 21(4):501-7. PMID: 19450960.
      Citations: 24     Fields:    Translation:Cells
    34. Ruiz-Canada C, Kelleher DJ, Gilmore R. Cotranslational and posttranslational N-glycosylation of polypeptides by distinct mammalian OST isoforms. Cell. 2009 Jan 23; 136(2):272-83. PMID: 19167329.
      Citations: 189     Fields:    Translation:HumansCells
    35. Magnelli P, Cipollo JF, Ratner DM, Cui J, Kelleher D, Gilmore R, Costello CE, Robbins PW, Samuelson J. Unique Asn-linked oligosaccharides of the human pathogen Entamoeba histolytica. J Biol Chem. 2008 Jun 27; 283(26):18355-64. PMID: 18417475.
      Citations: 18     Fields:    Translation:AnimalsCells
    36. Jiang Y, Cheng Z, Mandon EC, Gilmore R. An interaction between the SRP receptor and the translocon is critical during cotranslational protein translocation. J Cell Biol. 2008 Mar 24; 180(6):1149-61. PMID: 18347066.
      Citations: 35     Fields:    Translation:AnimalsCells
    37. Banerjee S, Vishwanath P, Cui J, Kelleher DJ, Gilmore R, Robbins PW, Samuelson J. The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation. Proc Natl Acad Sci U S A. 2007 Jul 10; 104(28):11676-81. PMID: 17606910.
      Citations: 70     Fields:    Translation:AnimalsCells
    38. Kelleher DJ, Banerjee S, Cura AJ, Samuelson J, Gilmore R. Dolichol-linked oligosaccharide selection by the oligosaccharyltransferase in protist and fungal organisms. J Cell Biol. 2007 Apr 09; 177(1):29-37. PMID: 17403929.
      Citations: 28     Fields:    Translation:AnimalsCells
    39. Mandon EC, Gilmore R. The tail end of membrane insertion. Cell. 2007 Mar 23; 128(6):1031-2. PMID: 17382875.
      Citations: 3     Fields:    Translation:AnimalsCells
    40. Cheng Z, Gilmore R. Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration. Nat Struct Mol Biol. 2006 Oct; 13(10):930-6. PMID: 16980973.
      Citations: 29     Fields:    Translation:Cells
    41. Kelleher DJ, Gilmore R. An evolving view of the eukaryotic oligosaccharyltransferase. Glycobiology. 2006 Apr; 16(4):47R-62R. PMID: 16317064.
      Citations: 234     Fields:    Translation:HumansAnimalsCells
    42. Karamyshev AL, Kelleher DJ, Gilmore R, Johnson AE, von Heijne G, Nilsson I. Mapping the interaction of the STT3 subunit of the oligosaccharyl transferase complex with nascent polypeptide chains. J Biol Chem. 2005 Dec 09; 280(49):40489-93. PMID: 16216884.
      Citations: 12     Fields:    Translation:AnimalsCells
    43. Samuelson J, Banerjee S, Magnelli P, Cui J, Kelleher DJ, Gilmore R, Robbins PW. The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases. Proc Natl Acad Sci U S A. 2005 Feb 01; 102(5):1548-53. PMID: 15665075.
      Citations: 116     Fields:    Translation:HumansAnimalsCells
    44. Cheng Z, Jiang Y, Mandon EC, Gilmore R. Identification of cytoplasmic residues of Sec61p involved in ribosome binding and cotranslational translocation. J Cell Biol. 2005 Jan 03; 168(1):67-77. PMID: 15631991.
      Citations: 45     Fields:    Translation:HumansAnimalsCells
    45. Mandon EC, Gilmore R. GTPase twins in the SRP family. Nat Struct Mol Biol. 2004 Feb; 11(2):115-6. PMID: 14749771.
      Citations:    Fields:    Translation:Cells
    46. Mandon EC, Jiang Y, Gilmore R. Dual recognition of the ribosome and the signal recognition particle by the SRP receptor during protein targeting to the endoplasmic reticulum. J Cell Biol. 2003 Aug 18; 162(4):575-85. PMID: 12913112.
      Citations: 19     Fields:    Translation:AnimalsCells
    47. Wu X, Rush JS, Karaoglu D, Krasnewich D, Lubinsky MS, Waechter CJ, Gilmore R, Freeze HH. Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij. Hum Mutat. 2003 Aug; 22(2):144-50. PMID: 12872255.
      Citations: 55     Fields:    Translation:HumansAnimalsCells
    48. Kelleher DJ, Karaoglu D, Mandon EC, Gilmore R. Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties. Mol Cell. 2003 Jul; 12(1):101-11. PMID: 12887896.
      Citations: 100     Fields:    Translation:HumansAnimalsCells
    49. Nilsson I, Kelleher DJ, Miao Y, Shao Y, Kreibich G, Gilmore R, von Heijne G, Johnson AE. Photocross-linking of nascent chains to the STT3 subunit of the oligosaccharyltransferase complex. J Cell Biol. 2003 May 26; 161(4):715-25. PMID: 12756234.
      Citations: 65     Fields:    Translation:AnimalsCells
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