Yifan Cheng, PhD

Title(s)Professor, Biochemistry and Biophysics
SchoolSchool of Medicine
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    Collapse Overview 
    Collapse Overview
    We are interested in studying the three-dimensional structures of macromolecular complexes: their structural architectures, the regulation of their function and the dynamic processes of their assembly and disassembly, by molecular electron microscopy (cryoEM). A full understanding of the biological functions/processes of any macromolecular complex requires structural information at a wide range of resolutions, including atomic details of its components, spatial arrangements of these components and interactions between them. CryoEM can be used to study macromolecules in their native conformations at a wide resolution range, from sub-nanometer resolution (single particle cryoEM) to the cellular level (electron tomography).

    Collapse Research 
    Collapse Research Activities and Funding
    Structural mechanism of integrin-mediated TGF-b activation
    NIH/NHLBI R01HL134183Jul 4, 2016 - Apr 30, 2020
    Role: Co-Principal Investigator
    Acquisition of an electron microscope for high-resolution single particle cryo-EM
    NIH S10OD021741May 1, 2016 - Apr 30, 2017
    Role: Principal Investigator
    Mapping the conformational cycle of transmembrane transporters
    NIH/NIGMS P01GM111126Aug 1, 2015 - Jul 31, 2020
    Role: Co-Investigator
    Linux cluster for near atomic resolution single particle cryo-EM
    NIH S10OD020054Apr 15, 2015 - Apr 14, 2016
    Role: Principal Investigator
    Structures and gating mechanisms of TRP ion channels
    NIH/NIGMS R01GM098672Aug 1, 2011 - Jun 30, 2019
    Role: Principal Investigator
    GPU Computing Enabled Linux Computer Cluster
    NIH/NCRR S10RR026814Jan 28, 2010 - Jan 27, 2012
    Role: Principal Investigator
    Mechanism of gate-opening in the 20S proteasome induced by the proteasomal ATPase
    NIH/NIGMS R01GM082893Jan 1, 2008 - Mar 31, 2018
    Role: Principal Investigator
    HARC Center: HIV Accessory and Regulatory Complexes
    NIH/NIGMS P50GM082250Aug 27, 2007 - Aug 31, 2022
    Role: Co-Investigator
    National Resource for Automated Molecular Microscopy
    NIH P41RR017573Sep 30, 2002 - Jul 31, 2012
    Role: Co-Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Cheng Y. Membrane protein structural biology in the era of single particle cryo-EM. Curr Opin Struct Biol. 2018 Oct; 52:58-63. PMID: 30219656.
      View in: PubMed
    2. Cheng Y. Single-Particle Cryo-EM at Crystallographic Resolution. Cell. 2015 Apr 23; 161(3):450-457. PMID: 25910205; PMCID: PMC4409662.
    3. Booth DS, Cheng Y, Frankel AD. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA. Elife. 2014 Dec 08; 3:e04121. PMID: 25486595; PMCID: PMC4360530.
    4. Bhabha G, Cheng HC, Zhang N, Moeller A, Liao M, Speir JA, Cheng Y, Vale RD. Allosteric communication in the dynein motor domain. Cell. 2014 Nov 06; 159(4):857-68. PMID: 25417161; PMCID: PMC4269335.
    5. Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB, Stiller SB, Robles-Colmanares Y, Stroud RM, Tampé R, Craik CS, Cheng Y. Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature. 2015 Jan 15; 517(7534):396-400. PMID: 25363761; PMCID: PMC4372080.
    6. Wang Y, Schnitzbauer J, Hu Z, Li X, Cheng Y, Huang ZL, Huang B. Localization events-based sample drift correction for localization microscopy with redundant cross-correlation algorithm. Opt Express. 2014 Jun 30; 22(13):15982-91. PMID: 24977854; PMCID: PMC4162368.
    7. Minagawa S, Lou J, Seed RI, Cormier A, Wu S, Cheng Y, Murray L, Tsui P, Connor J, Herbst R, Govaerts C, Barker T, Cambier S, Yanagisawa H, Goodsell A, Hashimoto M, Brand OJ, Cheng R, Ma R, McKnelly KJ, Wen W, Hill A, Jablons D, Wolters P, Kitamura H, Araya J, Barczak AJ, Erle DJ, Reichardt LF, Marks JD, Baron JL, Nishimura SL. Selective targeting of TGF-ß activation to treat fibroinflammatory airway disease. Sci Transl Med. 2014 Jun 18; 6(241):241ra79. PMID: 24944194; PMCID: PMC4341974.
    8. Liao M, Cao E, Julius D, Cheng Y. Single particle electron cryo-microscopy of a mammalian ion channel. Curr Opin Struct Biol. 2014 Aug; 27:1-7. PMID: 24681231; PMCID: PMC4176607.
    9. Lu J, Yu Y, Zhu I, Cheng Y, Sun PD. Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc Natl Acad Sci U S A. 2014 Apr 08; 111(14):5189-94. PMID: 24706838; PMCID: PMC3986191.
    10. Penczek PA, Fang J, Li X, Cheng Y, Loerke J, Spahn CM. CTER-rapid estimation of CTF parameters with error assessment. Ultramicroscopy. 2014 May; 140:9-19. PMID: 24562077; PMCID: PMC4016771.
    11. Liao M, Cao E, Julius D, Cheng Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature. 2013 Dec 05; 504(7478):107-12. PMID: 24305160; PMCID: PMC4078027.
    12. Cao E, Liao M, Cheng Y, Julius D. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature. 2013 Dec 05; 504(7478):113-8. PMID: 24305161; PMCID: PMC4023639.
    13. Asensio CS, Sirkis DW, Maas JW, Egami K, To TL, Brodsky FM, Shu X, Cheng Y, Edwards RH. Self-assembly of VPS41 promotes sorting required for biogenesis of the regulated secretory pathway. Dev Cell. 2013 Nov 25; 27(4):425-37. PMID: 24210660; PMCID: PMC3974617.
    14. Li X, Zheng SQ, Egami K, Agard DA, Cheng Y. Influence of electron dose rate on electron counting images recorded with the K2 camera. J Struct Biol. 2013 Nov; 184(2):251-60. PMID: 23968652; PMCID: PMC3854003.
    15. Qian MX, Pang Y, Liu CH, Haratake K, Du BY, Ji DY, Wang GF, Zhu QQ, Song W, Yu Y, Zhang XX, Huang HT, Miao S, Chen LB, Zhang ZH, Liang YN, Liu S, Cha H, Yang D, Zhai Y, Komatsu T, Tsuruta F, Li H, Cao C, Li W, Li GH, Cheng Y, Chiba T, Wang L, Goldberg AL, Shen Y, Qiu XB. Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis. Cell. 2013 May 23; 153(5):1012-24. PMID: 23706739; PMCID: PMC3983474.
    16. Park S, Li X, Kim HM, Singh CR, Tian G, Hoyt MA, Lovell S, Battaile KP, Zolkiewski M, Coffino P, Roelofs J, Cheng Y, Finley D. Reconfiguration of the proteasome during chaperone-mediated assembly. Nature. 2013 May 23; 497(7450):512-6. PMID: 23644457; PMCID: PMC3687086.
    17. Li X, Mooney P, Zheng S, Booth CR, Braunfeld MB, Gubbens S, Agard DA, Cheng Y. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat Methods. 2013 Jun; 10(6):584-90. PMID: 23644547; PMCID: PMC3684049.
    18. Canzio D, Liao M, Naber N, Pate E, Larson A, Wu S, Marina DB, Garcia JF, Madhani HD, Cooke R, Schuck P, Cheng Y, Narlikar GJ. A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly. Nature. 2013 Apr 18; 496(7445):377-81. PMID: 23485968; PMCID: PMC3907283.
    19. Avila-Sakar A, Li X, Zheng SQ, Cheng Y. Recording high-resolution images of two-dimensional crystals of membrane proteins. Methods Mol Biol. 2013; 955:129-52. PMID: 23132059.
      View in: PubMed
    20. Schneidman-Duhovny D, Rossi A, Avila-Sakar A, Kim SJ, Velázquez-Muriel J, Strop P, Liang H, Krukenberg KA, Liao M, Kim HM, Sobhanifar S, Dötsch V, Rajpal A, Pons J, Agard DA, Cheng Y, Sali A. A method for integrative structure determination of protein-protein complexes. Bioinformatics. 2012 Dec 15; 28(24):3282-9. PMID: 23093611; PMCID: PMC3519461.
    21. Martinez-Avila O, Wu S, Kim SJ, Cheng Y, Khan F, Samudrala R, Sali A, Horst JA, Habelitz S. Self-assembly of filamentous amelogenin requires calcium and phosphate: from dimers via nanoribbons to fibrils. Biomacromolecules. 2012 Nov 12; 13(11):3494-502. PMID: 22974364; PMCID: PMC3496023.
    22. Wu S, Avila-Sakar A, Kim J, Booth DS, Greenberg CH, Rossi A, Liao M, Li X, Alian A, Griner SL, Juge N, Yu Y, Mergel CM, Chaparro-Riggers J, Strop P, Tampé R, Edwards RH, Stroud RM, Craik CS, Cheng Y. Fabs enable single particle cryoEM studies of small proteins. Structure. 2012 Apr 04; 20(4):582-92. PMID: 22483106.
      View in: PubMed
    23. Booth DS, Avila-Sakar A, Cheng Y. Visualizing proteins and macromolecular complexes by negative stain EM: from grid preparation to image acquisition. J Vis Exp. 2011 Dec 22; (58). PMID: 22215030.
      View in: PubMed
    24. Martinez-Avila OM, Wu S, Cheng Y, Lee R, Khan F, Habelitz S. Self-assembly of amelogenin proteins at the water-oil interface. Eur J Oral Sci. 2011 Dec; 119 Suppl 1:75-82. PMID: 22243231.
      View in: PubMed
    25. Nakamura K, Nemani VM, Azarbal F, Skibinski G, Levy JM, Egami K, Munishkina L, Zhang J, Gardner B, Wakabayashi J, Sesaki H, Cheng Y, Finkbeiner S, Nussbaum RL, Masliah E, Edwards RH. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J Biol Chem. 2011 Jun 10; 286(23):20710-26. PMID: 21489994.
      View in: PubMed
    26. Zheng SQ, Branlund E, Kesthelyi B, Braunfeld MB, Cheng Y, Sedat JW, Agard DA. A distributed multi-GPU system for high speed electron microscopic tomographic reconstruction. Ultramicroscopy. 2011 Jul; 111(8):1137-43. PMID: 21741915; PMCID: PMC3190582.
    27. He X, Wu S, Martinez-Avila O, Cheng Y, Habelitz S. Self-aligning amelogenin nanoribbons in oil-water system. J Struct Biol. 2011 Apr; 174(1):203-12. PMID: 21134461; PMCID: PMC3204882.
    28. Kim HM, Yu Y, Cheng Y. Structure characterization of the 26S proteasome. Biochim Biophys Acta. 2011 Feb; 1809(2):67-79. PMID: 20800708; PMCID: PMC3010250.
    29. Daugherty MD, Booth DS, Jayaraman B, Cheng Y, Frankel AD. HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes. Proc Natl Acad Sci U S A. 2010 Jul 13; 107(28):12481-6. PMID: 20616058.
      View in: PubMed
    30. Li X, Grigorieff N, Cheng Y. GPU-enabled FREALIGN: accelerating single particle 3D reconstruction and refinement in Fourier space on graphics processors. J Struct Biol. 2010 Dec; 172(3):407-12. PMID: 20558298; PMCID: PMC2964447.
    31. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, Krogan NJ, Plemenitas A, Peterlin BM. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic. 2010 Jan; 11(1):110-22. PMID: 19912576; PMCID: PMC2796297.
    32. Hite RK, Schenk AD, Li Z, Cheng Y, Walz T. Collecting electron crystallographic data of two-dimensional protein crystals. Methods Enzymol. 2010; 481:251-82. PMID: 20887861.
      View in: PubMed
    33. Racki LR, Yang JG, Naber N, Partensky PD, Acevedo A, Purcell TJ, Cooke R, Cheng Y, Narlikar GJ. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature. 2009 Dec 24; 462(7276):1016-21. PMID: 20033039; PMCID: PMC2869534.
    34. Yu Y, Smith DM, Kim HM, Rodriguez V, Goldberg AL, Cheng Y. Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions. EMBO J. 2010 Feb 03; 29(3):692-702. PMID: 20019667; PMCID: PMC2830694.
    35. Li Z, Hite RK, Cheng Y, Walz T. Evaluation of imaging plates as recording medium for images of negatively stained single particles and electron diffraction patterns of two-dimensional crystals. J Electron Microsc (Tokyo). 2010; 59(1):53-63. PMID: 19643814; PMCID: PMC3156676.
    36. Cheng Y. Toward an atomic model of the 26S proteasome. Curr Opin Struct Biol. 2009 Apr; 19(2):203-8. PMID: 19286367; PMCID: PMC2743420.
    37. Kim HZ, Jung K, Kim HM, Cheng Y, Koh GY. A designed angiopoietin-2 variant, pentameric COMP-Ang2, strongly activates Tie2 receptor and stimulates angiogenesis. Biochim Biophys Acta. 2009 May; 1793(5):772-80. PMID: 19339208.
      View in: PubMed
    38. Cheng Y, Walz T. The advent of near-atomic resolution in single-particle electron microscopy. Annu Rev Biochem. 2009; 78:723-42. PMID: 19489732.
      View in: PubMed
    39. Rabl J, Smith DM, Yu Y, Chang SC, Goldberg AL, Cheng Y. Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases. Mol Cell. 2008 May 09; 30(3):360-8. PMID: 18471981; PMCID: PMC4141531.
    40. Frey G, Peng H, Rits-Volloch S, Morelli M, Cheng Y, Chen B. A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies. Proc Natl Acad Sci U S A. 2008 Mar 11; 105(10):3739-44. PMID: 18322015; PMCID: PMC2268799.
    41. Ballister ER, Lai AH, Zuckermann RN, Cheng Y, Mougous JD. In vitro self-assembly of tailorable nanotubes from a simple protein building block. Proc Natl Acad Sci U S A. 2008 Mar 11; 105(10):3733-8. PMID: 18310321; PMCID: PMC2268831.
    42. Ohi MD, Feoktistova A, Ren L, Yip C, Cheng Y, Chen JS, Yoon HJ, Wall JS, Huang Z, Penczek PA, Gould KL, Walz T. Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1. Mol Cell. 2007 Dec 14; 28(5):871-85. PMID: 18082611; PMCID: PMC2197158.
    43. Gonen T, Hite RK, Cheng Y, Petre BM, Kistler J, Walz T. Polymorphic assemblies and crystalline arrays of lens tetraspanin MP20. J Mol Biol. 2008 Feb 15; 376(2):380-92. PMID: 18166196.
      View in: PubMed
    44. Smith DM, Chang SC, Park S, Finley D, Cheng Y, Goldberg AL. Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry. Mol Cell. 2007 Sep 07; 27(5):731-44. PMID: 17803938; PMCID: PMC2083707.
    45. Cheng Y, Walz T. Reconstructing the endocytotic machinery. Methods Cell Biol. 2007; 79:463-87. PMID: 17327169.
      View in: PubMed
    46. Cheng Y, Boll W, Kirchhausen T, Harrison SC, Walz T. Cryo-electron tomography of clathrin-coated vesicles: structural implications for coat assembly. J Mol Biol. 2007 Jan 19; 365(3):892-9. PMID: 17095010; PMCID: PMC1839968.
    47. Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer TA. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006 Oct; 25(4):583-94. PMID: 17045822.
      View in: PubMed
    48. Liu J, Wu S, Reedy MC, Winkler H, Lucaveche C, Cheng Y, Reedy MK, Taylor KA. Electron tomography of swollen rigor fibers of insect flight muscle reveals a short and variably angled S2 domain. J Mol Biol. 2006 Sep 29; 362(4):844-60. PMID: 16949613.
      View in: PubMed
    49. Fotin A, Kirchhausen T, Grigorieff N, Harrison SC, Walz T, Cheng Y. Structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy. J Struct Biol. 2006 Dec; 156(3):453-60. PMID: 16908193; PMCID: PMC2910098.
    50. Nakagawa T, Cheng Y, Sheng M, Walz T. Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biol Chem. 2006 Feb; 387(2):179-87. PMID: 16497150.
      View in: PubMed
    51. Smith DM, Kafri G, Cheng Y, Ng D, Walz T, Goldberg AL. ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. Mol Cell. 2005 Dec 09; 20(5):687-98. PMID: 16337593.
      View in: PubMed
    52. Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Walz T. Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. Nature. 2005 Dec 01; 438(7068):633-8. PMID: 16319884; PMCID: PMC1350984.
    53. Cheng Y, Wolf E, Larvie M, Zak O, Aisen P, Grigorieff N, Harrison SC, Walz T. Single particle reconstructions of the transferrin-transferrin receptor complex obtained with different specimen preparation techniques. J Mol Biol. 2006 Feb 03; 355(5):1048-65. PMID: 16343539.
      View in: PubMed
    54. Cheng Y, Zak O, Aisen P, Harrison SC, Walz T. Single particle reconstruction of the human apo-transferrin-transferrin receptor complex. J Struct Biol. 2005 Dec; 152(3):204-10. PMID: 16343946.
      View in: PubMed
    55. Nakagawa T, Cheng Y, Ramm E, Sheng M, Walz T. Structure and different conformational states of native AMPA receptor complexes. Nature. 2005 Feb 03; 433(7025):545-9. PMID: 15690046.
      View in: PubMed
    56. Fotin A, Cheng Y, Sliz P, Grigorieff N, Harrison SC, Kirchhausen T, Walz T. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature. 2004 Dec 02; 432(7017):573-9. PMID: 15502812.
      View in: PubMed
    57. Fotin A, Cheng Y, Grigorieff N, Walz T, Harrison SC, Kirchhausen T. Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating. Nature. 2004 Dec 02; 432(7017):649-53. PMID: 15502813.
      View in: PubMed
    58. Gonen T, Cheng Y, Kistler J, Walz T. Aquaporin-0 membrane junctions form upon proteolytic cleavage. J Mol Biol. 2004 Sep 24; 342(4):1337-45. PMID: 15351655.
      View in: PubMed
    59. Gonen T, Sliz P, Kistler J, Cheng Y, Walz T. Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature. 2004 May 13; 429(6988):193-7. PMID: 15141214.
      View in: PubMed
    60. Chen B, Cheng Y, Calder L, Harrison SC, Reinherz EL, Skehel JJ, Wiley DC. A chimeric protein of simian immunodeficiency virus envelope glycoprotein gp140 and Escherichia coli aspartate transcarbamoylase. J Virol. 2004 May; 78(9):4508-16. PMID: 15078931; PMCID: PMC387710.
    61. Ohi M, Li Y, Cheng Y, Walz T. Negative Staining and Image Classification - Powerful Tools in Modern Electron Microscopy. Biol Proced Online. 2004; 6:23-34. PMID: 15103397.
      View in: PubMed
    62. Cheng Y, Zak O, Aisen P, Harrison SC, Walz T. Structure of the human transferrin receptor-transferrin complex. Cell. 2004 Feb 20; 116(4):565-76. PMID: 14980223.
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    63. Toth EA, Li Y, Sawaya MR, Cheng Y, Ellenberger T. The crystal structure of the bifunctional primase-helicase of bacteriophage T7. Mol Cell. 2003 Nov; 12(5):1113-23. PMID: 14636571.
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    64. Lederkremer GZ, Cheng Y, Petre BM, Vogan E, Springer S, Schekman R, Walz T, Kirchhausen T. Structure of the Sec23p/24p and Sec13p/31p complexes of COPII. Proc Natl Acad Sci U S A. 2001 Sep 11; 98(19):10704-9. PMID: 11535824; PMCID: PMC58530.
    65. Schmidt-Krey I, Mitsuoka K, Hirai T, Murata K, Cheng Y, Fujiyoshi Y, Morgenstern R, Hebert H. The three-dimensional map of microsomal glutathione transferase 1 at 6 A resolution. EMBO J. 2000 Dec 01; 19(23):6311-6. PMID: 11101503; PMCID: PMC305867.
    66. Schmidt-Krey I, Murata K, Hirai T, Mitsuoka K, Cheng Y, Morgenstern R, Fujiyoshi Y, Hebert H. The projection structure of the membrane protein microsomal glutathione transferase at 3 A resolution as determined from two-dimensional hexagonal crystals. J Mol Biol. 1999 Apr 30; 288(2):243-53. PMID: 10329140.
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    67. Hiroaki Y, Mitsuoka K, Cheng Y, Hiroaki H, Fujiyoshi Y. Influence of various nucleotides on the in situ crystallization of Ca2+-ATPase. Biochim Biophys Acta. 1999 Jan 08; 1415(2):361-8. PMID: 9889398.
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    68. Cheng Y, Taylor KA. Characterization of the low magnification performance of a Philips CM300-FEG. Ultramicroscopy. 1998 Sep; 74(4):209-20. PMID: 9809458.
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    69. Taylor KA, Tang J, Cheng Y, Winkler H. The use of electron tomography for structural analysis of disordered protein arrays. J Struct Biol. 1997 Dec; 120(3):372-86. PMID: 9441940.
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