Computed structures of core eukaryotic protein complexes.

Journal: Science (New York, N.Y.)
PMID: 34762488

Abstract

Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take advantage of advances in proteome-wide amino acid coevolution analysis and deep-learning–based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes within the proteome. We use a combination of RoseTTAFold and AlphaFold to screen through paired multiple sequence alignments for 8.3 million pairs of yeast proteins, identify 1505 likely to interact, and build structure models for 106 previously unidentified assemblies and 806 that have not been structurally characterized. These complexes, which have as many as five subunits, play roles in almost all key processes in eukaryotic cells and provide broad insights into biological function.

Authors

  • Ian R Humphreys
    Department of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington, USA.
  • Jimin Pei
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Minkyung Baek
    Department of Biochemistry and Institute for Protein Design, University of Washington, Washington, WA, USA.
  • Aditya Krishnakumar
    Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Ivan Anishchenko
    Computational Biology Program, The University of Kansas, Lawrence, Kansas.
  • Sergey Ovchinnikov
    Center for Systems Biology, Harvard University, Cambridge, MA 02138, United States.
  • Jing Zhang
    MOEMIL Laboratory, School of Optoelectronic Information, University of Electronic Science and Technology of China, Chengdu, China.
  • Travis J Ness
    Department of Chemistry, Wayne State University, Detroit, MI, USA.
  • Sudeep Banjade
    Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Saket R Bagde
    Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Viktoriya G Stancheva
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Xiao-Han Li
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Kaixian Liu
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zhi Zheng
    Department of Chemical Engineering, School of Chemistry and Chemical Engineering, Nanjing University.
  • Daniel J Barrero
    Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Upasana Roy
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
  • Jochen Kuper
    Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.
  • Israel S Fernández
    Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Barnabas Szakal
    IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
  • Dana Branzei
    IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
  • Josep Rizo
    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Caroline Kisker
    Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.
  • Eric C Greene
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
  • Sue Biggins
    Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Scott Keeney
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Elizabeth A Miller
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • J Christopher Fromme
    Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Tamara L Hendrickson
    Department of Chemistry, Wayne State University, Detroit, MI, USA.
  • Qian Cong
    Department of Biochemistry, Seattle, WA 98105, USA.
  • David Baker
    Department of Biochemistry, University of Washington, Seattle, Washington.

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