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Andrei A Korostelev PhD

TitleProfessor
InstitutionUMass Chan Medical School
DepartmentRNA Therapeutics Institute
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-2353
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentRNA Therapeutics Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBioinformatics and Computational Biology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program


    Collapse Biography 
    Collapse education and training
    Moscow State University, Moscow, , Russian FederationBSChemistry
    Moscow State University, Moscow, , Russian FederationMSChemistry
    Florida State University- Tallahassee, Tallahassee, FL, United StatesPHDChemistry & Biochemistry
    Collapse awards and honors
    1994 - 1995Soros Academic Fellowship, Moscow State University
    1996 - 1997I.V. Berezin Young Scientist Award, Moscow State University
    2010The RNA Society / Scaringe Young Scientist Award, runner-up, RNA Society
    2018Earl and Thressa Stadtman Scholar Award, ASBMB (American Society for Biochemistry and Molecular Biology)
    2018Early Career Award, RNA Society

    Collapse Overview 
    Collapse overview

    Structure and Function of the Ribosome

    Visit Korostelev Lab Web Page

    Dr.  Andrei Korostelev, Ph.D.

    Ribosomes, the ancient and universal cellular machines, are responsible for decoding genetic information and synthesizing proteins in all living organisms. A eubacterial ribosome has a molecular weight of approximately 2.5 MDa and consists of about 55 proteins and 3 large RNA molecules. So far, the ribosome is the largest asymmetric macromolecule amenable to crystallographic analyses.

    The multi-step process of translation is not fully understood: only recently, structural details of some steps of translation started to emerge.

    In our lab, we aim at a full structural description of the highly dynamic process of translation. We use X-ray crystallography to obtain snapshots of different functional states of the ribosome and biochemistry to test the hypotheses concerning the mechanisms and dynamics of the ribosome and translation factors. These studies are designed not only to expand our fundamental knowledge of this molecular machine but also to aid in the development of new drugs that target ribosomes.

    Translation termination on the 70S ribosome

    Translation termination on the 70S ribosome.Release factor RF2 (yellow) is bound to the ribosome in response to a stop codon encoded in a messenger RNA (green) located on the small 30S ribosomal subunit (cyan and blue). RF2 is positioned to catalyze the hydrolysis of a peptidyl-tRNA (green and orange) on the large 50S subunit (grey, purple and magenta). An E-site-bound tRNA is in red.

    This structural model was rendered in Pymol and is based on the X-ray structures of 70S translation termination complexes (Korostelev et al., 2008; Laurberg et al., 2008) and a 70S-tRNA complex (Jenner et al., 2010).


    Collapse Rotation Projects

    Rotation projects

    We apply X-ray crystallography and biochemical methods to understand the mechanisms employed by the ribosome. Potential rotation projects are 1) to understand various aspects of translation via mutagenesis/biochemical assays, 2) to crystallize and work on determining the structures of translation factors and functional ribosome complexes, and 3) to improve computational methods used to determine crystal structures of macromolecules.

    Feel free to contact the lab for a more detailed discussion.



    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. Loveland AB, Svidritskiy E, Susorov D, Lee S, Park A, Zvornicanin S, Demo G, Gao FB, Korostelev AA. Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM. Nat Commun. 2022 May 19; 13(1):2776. PMID: 35589706.
      Citations:    Fields:    Translation:HumansCells
    2. Korostelev AA. The Structural Dynamics of Translation. Annu Rev Biochem. 2022 Jun 21; 91:245-267. PMID: 35287473.
      Citations:    Fields:    
    3. Carbone CE, Loveland AB, Gamper HB, Hou YM, Demo G, Korostelev AA. Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP. Nat Commun. 2021 12 13; 12(1):7236. PMID: 34903725.
      Citations: 4     Fields:    Translation:Cells
    4. Korostelev AA. Diversity and Similarity of Termination and Ribosome Rescue in Bacterial, Mitochondrial, and Cytoplasmic Translation. Biochemistry (Mosc). 2021 Sep; 86(9):1107-1121. PMID: 34565314.
      Citations:    Fields:    Translation:Cells
    5. Demo G, Gamper HB, Loveland AB, Masuda I, Carbone CE, Svidritskiy E, Hou YM, Korostelev AA. Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation. Nat Commun. 2021 07 30; 12(1):4644. PMID: 34330903.
      Citations: 5     Fields:    Translation:Cells
    6. Carbone CE, Demo G, Madireddy R, Svidritskiy E, Korostelev AA. ArfB can displace mRNA to rescue stalled ribosomes. Nat Commun. 2020 11 03; 11(1):5552. PMID: 33144582.
      Citations: 5     Fields:    Translation:Cells
    7. Susorov D, Egri S, Korostelev AA. Termi-Luc: a versatile assay to monitor full-protein release from ribosomes. RNA. 2020 12; 26(12):2044-2050. PMID: 32817446.
      Citations: 4     Fields:    Translation:HumansAnimalsCells
    8. Loveland AB, Demo G, Korostelev AA. Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading. Nature. 2020 08; 584(7822):640-645. PMID: 32612237.
      Citations: 25     Fields:    Translation:Cells
    9. Hsu HL, Brown A, Loveland AB, Lotun A, Xu M, Luo L, Xu G, Li J, Ren L, Su Q, Gessler DJ, Wei Y, Tai PWL, Korostelev AA, Gao G. Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties. Nat Commun. 2020 06 30; 11(1):3279. PMID: 32606306.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    10. Huang S, Aleksashin NA, Loveland AB, Klepacki D, Reier K, Kefi A, Szal T, Remme J, Jaeger L, Vázquez-Laslop N, Korostelev AA, Mankin AS. Ribosome engineering reveals the importance of 5S rRNA autonomy for ribosome assembly. Nat Commun. 2020 06 09; 11(1):2900. PMID: 32518240.
      Citations: 5     Fields:    Translation:Cells
    11. Bao C, Loerch S, Ling C, Korostelev AA, Grigorieff N, Ermolenko DN. mRNA stem-loops can pause the ribosome by hindering A-site tRNA binding. Elife. 2020 05 19; 9. PMID: 32427100.
      Citations: 11     Fields:    Translation:Cells
    12. Svidritskiy E, Demo G, Loveland AB, Xu C, Korostelev AA. Extensive ribosome and RF2 rearrangements during translation termination. Elife. 2019 09 12; 8. PMID: 31513010.
      Citations: 12     Fields:    Translation:Cells
    13. Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT. The Genetic Landscape of Diamond-Blackfan Anemia. Am J Hum Genet. 2019 Feb 07; 104(2):356. PMID: 30735661.
      Citations: 7     Fields:    
    14. Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT. The Genetic Landscape of Diamond-Blackfan Anemia. Am J Hum Genet. 2018 12 06; 103(6):930-947. PMID: 30503522.
      Citations: 72     Fields:    Translation:HumansCells
    15. Svidritskiy E, Demo G, Korostelev AA. Mechanism of premature translation termination on a sense codon. J Biol Chem. 2018 08 10; 293(32):12472-12479. PMID: 29941456.
      Citations: 9     Fields:    Translation:Cells
    16. Svidritskiy E, Korostelev AA. Conformational Control of Translation Termination on the 70S Ribosome. Structure. 2018 06 05; 26(6):821-828.e3. PMID: 29731232.
      Citations: 13     Fields:    Translation:Cells
    17. Svidritskiy E, Korostelev AA. Mechanism of Inhibition of Translation Termination by Blasticidin S. J Mol Biol. 2018 03 02; 430(5):591-593. PMID: 29366636.
      Citations: 7     Fields:    Translation:Cells
    18. Loveland AB, Korostelev AA. Structural dynamics of protein S1 on the 70S ribosome visualized by ensemble cryo-EM. Methods. 2018 03 15; 137:55-66. PMID: 29247757.
      Citations: 23     Fields:    Translation:Cells
    19. Demo G, Rasouly A, Vasilyev N, Svetlov V, Loveland AB, Diaz-Avalos R, Grigorieff N, Nudler E, Korostelev AA. Structure of RNA polymerase bound to ribosomal 30S subunit. Elife. 2017 10 13; 6. PMID: 29027901.
      Citations: 39     Fields:    Translation:Cells
    20. Loveland AB, Demo G, Grigorieff N, Korostelev AA. Ensemble cryo-EM elucidates the mechanism of translation fidelity. Nature. 2017 06 01; 546(7656):113-117. PMID: 28538735.
      Citations: 69     Fields:    Translation:Cells
    21. Koh CS, Madireddy R, Beane TJ, Zamore PD, Korostelev AA. Small methyltransferase RlmH assembles a composite active site to methylate a ribosomal pseudouridine. Sci Rep. 2017 04 20; 7(1):969. PMID: 28428565.
      Citations: 6     Fields:    Translation:Cells
    22. Demo G, Svidritskiy E, Madireddy R, Diaz-Avalos R, Grant T, Grigorieff N, Sousa D, Korostelev AA. Mechanism of ribosome rescue by ArfA and RF2. Elife. 2017 03 16; 6. PMID: 28300532.
      Citations: 24     Fields:    Translation:Cells
    23. Loveland AB, Bah E, Madireddy R, Zhang Y, Brilot AF, Grigorieff N, Korostelev AA. Ribosome•RelA structures reveal the mechanism of stringent response activation. Elife. 2016 07 19; 5. PMID: 27434674.
      Citations: 65     Fields:    Translation:Cells
    24. Abeyrathne PD, Koh CS, Grant T, Grigorieff N, Korostelev AA. Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome. Elife. 2016 05 09; 5. PMID: 27159452.
      Citations: 56     Fields:    Translation:AnimalsCells
    25. Svidritskiy E, Madireddy R, Korostelev AA. Structural Basis for Translation Termination on a Pseudouridylated Stop Codon. J Mol Biol. 2016 05 22; 428(10 Pt B):2228-36. PMID: 27107638.
      Citations: 18     Fields:    Translation:Cells
    26. Tek A, Korostelev AA, Flores SC. MMB-GUI: a fast morphing method demonstrates a possible ribosomal tRNA translocation trajectory. Nucleic Acids Res. 2016 Jan 08; 44(1):95-105. PMID: 26673695.
      Citations: 7     Fields:    Translation:Cells
    27. Svidritskiy E, Korostelev AA. Ribosome Structure Reveals Preservation of Active Sites in the Presence of a P-Site Wobble Mismatch. Structure. 2015 Nov 03; 23(11):2155-61. PMID: 26412335.
      Citations: 7     Fields:    Translation:Cells
    28. Colussi TM, Costantino DA, Zhu J, Donohue JP, Korostelev AA, Jaafar ZA, Plank TD, Noller HF, Kieft JS. Initiation of translation in bacteria by a structured eukaryotic IRES RNA. Nature. 2015 Mar 05; 519(7541):110-3. PMID: 25652826.
      Citations: 23     Fields:    Translation:AnimalsCells
    29. Korostelev AA. A deeper look into translation initiation. Cell. 2014 Oct 23; 159(3):475-6. PMID: 25417100.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    30. Svidritskiy E, Brilot AF, Koh CS, Grigorieff N, Korostelev AA. Structures of yeast 80S ribosome-tRNA complexes in the rotated and nonrotated conformations. Structure. 2014 Aug 05; 22(8):1210-1218. PMID: 25043550.
      Citations: 41     Fields:    Translation:Cells
    31. Koh CS, Brilot AF, Grigorieff N, Korostelev AA. Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA-like structural element in the ribosomal decoding center. Proc Natl Acad Sci U S A. 2014 Jun 24; 111(25):9139-44. PMID: 24927574.
      Citations: 36     Fields:    Translation:Cells
    32. Brilot AF, Korostelev AA, Ermolenko DN, Grigorieff N. Structure of the ribosome with elongation factor G trapped in the pretranslocation state. Proc Natl Acad Sci U S A. 2013 Dec 24; 110(52):20994-9. PMID: 24324137.
      Citations: 79     Fields:    Translation:Cells
    33. Svidritskiy E, Ling C, Ermolenko DN, Korostelev AA. Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome. Proc Natl Acad Sci U S A. 2013 Jul 23; 110(30):12283-8. PMID: 23824292.
      Citations: 42     Fields:    Translation:Cells
    34. Santos N, Zhu J, Donohue JP, Korostelev AA, Noller HF. Crystal structure of the 70S ribosome bound with the Q253P mutant form of release factor RF2. Structure. 2013 Jul 02; 21(7):1258-63. PMID: 23769667.
      Citations: 18     Fields:    Translation:Cells
    35. Zhou J, Korostelev A, Lancaster L, Noller HF. Crystal structures of 70S ribosomes bound to release factors RF1, RF2 and RF3. Curr Opin Struct Biol. 2012 Dec; 22(6):733-42. PMID: 22999888.
      Citations: 19     Fields:    Translation:Cells
    36. Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P. Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1. BMC Biol. 2011 Jul 06; 9:48. PMID: 21729334.
      Citations: 31     Fields:    Translation:Cells
    37. Korennykh AV, Korostelev AA, Egea PF, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P. Structural and functional basis for RNA cleavage by Ire1. BMC Biol. 2011 Jul 06; 9:47. PMID: 21729333.
      Citations: 39     Fields:    Translation:Cells
    38. Korostelev AA. Structural aspects of translation termination on the ribosome. RNA. 2011 Aug; 17(8):1409-21. PMID: 21700725.
      Citations: 48     Fields:    Translation:HumansAnimalsCells
    39. Zhu J, Korostelev A, Costantino DA, Donohue JP, Noller HF, Kieft JS. Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome. Proc Natl Acad Sci U S A. 2011 Feb 01; 108(5):1839-44. PMID: 21245352.
      Citations: 26     Fields:    Translation:Cells
    40. Korostelev A, Zhu J, Asahara H, Noller HF. Recognition of the amber UAG stop codon by release factor RF1. EMBO J. 2010 Aug 04; 29(15):2577-85. PMID: 20588254.
      Citations: 57     Fields:    Translation:Cells
    41. Korostelev A, Laurberg M, Noller HF. Multistart simulated annealing refinement of the crystal structure of the 70S ribosome. Proc Natl Acad Sci U S A. 2009 Oct 27; 106(43):18195-200. PMID: 19822758.
      Citations: 5     Fields:    Translation:Cells
    42. Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Zhang C, Shokat KM, Stroud RM, Walter P. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009 Feb 05; 457(7230):687-93. PMID: 19079236.
      Citations: 307     Fields:    Translation:AnimalsCells
    43. Korostelev A, Asahara H, Lancaster L, Laurberg M, Hirschi A, Zhu J, Trakhanov S, Scott WG, Noller HF. Crystal structure of a translation termination complex formed with release factor RF2. Proc Natl Acad Sci U S A. 2008 Dec 16; 105(50):19684-9. PMID: 19064930.
      Citations: 127     Fields:    Translation:Cells
    44. Korostelev A, Ermolenko DN, Noller HF. Structural dynamics of the ribosome. Curr Opin Chem Biol. 2008 Dec; 12(6):674-83. PMID: 18848900.
      Citations: 82     Fields:    Translation:Cells
    45. Laurberg M, Asahara H, Korostelev A, Zhu J, Trakhanov S, Noller HF. Structural basis for translation termination on the 70S ribosome. Nature. 2008 Aug 14; 454(7206):852-7. PMID: 18596689.
      Citations: 177     Fields:    Translation:Cells
    46. Korostelev A, Trakhanov S, Asahara H, Laurberg M, Lancaster L, Noller HF. Interactions and dynamics of the Shine Dalgarno helix in the 70S ribosome. Proc Natl Acad Sci U S A. 2007 Oct 23; 104(43):16840-3. PMID: 17940016.
      Citations: 39     Fields:    Translation:Cells
    47. Korostelev A, Noller HF. The ribosome in focus: new structures bring new insights. Trends Biochem Sci. 2007 Sep; 32(9):434-41. PMID: 17764954.
      Citations: 43     Fields:    Translation:HumansAnimalsCells
    48. Korostelev A, Noller HF. Analysis of structural dynamics in the ribosome by TLS crystallographic refinement. J Mol Biol. 2007 Nov 02; 373(4):1058-70. PMID: 17897673.
      Citations: 23     Fields:    Translation:Cells
    49. Korostelev A, Trakhanov S, Laurberg M, Noller HF. Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions and rearrangements. Cell. 2006 Sep 22; 126(6):1065-77. PMID: 16962654.
      Citations: 251     Fields:    Translation:Cells
    50. Murray S, Nilsson CL, Hare JT, Emmett MR, Korostelev A, Ongley H, Marshall AG, Chapman MS. Characterization of the capsid protein glycosylation of adeno-associated virus type 2 by high-resolution mass spectrometry. J Virol. 2006 Jun; 80(12):6171-6. PMID: 16731956.
      Citations: 9     Fields:    Translation:HumansCells
    51. Fabiola F, Korostelev A, Chapman MS. Bias in cross-validated free R factors: mitigation of the effects of non-crystallographic symmetry. Acta Crystallogr D Biol Crystallogr. 2006 Mar; 62(Pt 3):227-38. PMID: 16510969.
      Citations: 19     Fields:    Translation:Cells
    52. Korostelev A, Fenley MO, Chapman MS. Impact of a Poisson-Boltzmann electrostatic restraint on protein structures refined at medium resolution. Acta Crystallogr D Biol Crystallogr. 2004 Oct; 60(Pt 10):1786-94. PMID: 15388925.
      Citations: 4     Fields:    
    53. Gao H, Sengupta J, Valle M, Korostelev A, Eswar N, Stagg SM, Van Roey P, Agrawal RK, Harvey SC, Sali A, Chapman MS, Frank J. Study of the structural dynamics of the E coli 70S ribosome using real-space refinement. Cell. 2003 Jun 13; 113(6):789-801. PMID: 12809609.
      Citations: 112     Fields:    Translation:Cells
    54. Lima S, Hildenbrand J, Korostelev A, Hattman S, Li H. Crystal structure of an RNA helix recognized by a zinc-finger protein: an 18-bp duplex at 1.6 A resolution. RNA. 2002 Jul; 8(7):924-32. PMID: 12166647.
      Citations: 7     Fields:    Translation:Cells
    55. Fabiola F, Bertram R, Korostelev A, Chapman MS. An improved hydrogen bond potential: impact on medium resolution protein structures. Protein Sci. 2002 Jun; 11(6):1415-23. PMID: 12021440.
      Citations: 44     Fields:    Translation:HumansAnimalsCells
    56. Korostelev A, Bertram R, Chapman MS. Simulated-annealing real-space refinement as a tool in model building. Acta Crystallogr D Biol Crystallogr. 2002 May; 58(Pt 5):761-7. PMID: 11976486.
      Citations: 29     Fields:    Translation:Cells
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