An atlas of protein homo-oligomerization across domains of life.

Journal: Cell
PMID: 38325366

Abstract

Protein structures are essential to understanding cellular processes in molecular detail. While advances in artificial intelligence revealed the tertiary structure of proteins at scale, their quaternary structure remains mostly unknown. We devise a scalable strategy based on AlphaFold2 to predict homo-oligomeric assemblies across four proteomes spanning the tree of life. Our results suggest that approximately 45% of an archaeal proteome and a bacterial proteome and 20% of two eukaryotic proteomes form homomers. Our predictions accurately capture protein homo-oligomerization, recapitulate megadalton complexes, and unveil hundreds of homo-oligomer types, including three confirmed experimentally by structure determination. Integrating these datasets with omics information suggests that a majority of known protein complexes are symmetric. Finally, these datasets provide a structural context for interpreting disease mutations and reveal coiled-coil regions as major enablers of quaternary structure evolution in human. Our strategy is applicable to any organism and provides a comprehensive view of homo-oligomerization in proteomes.

Authors

  • Hugo Schweke
    Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Martin Pačesa
    Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland. m.pacesa@bioc.uzh.ch.
  • Tal Levin
    Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Casper A Goverde
    Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Prasun Kumar
    School of Chemistry, University of Bristol, Bristol BS8 1TS, UK; School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK; Bristol BioDesign Institute, University of Bristol, Life Sciences Building, Bristol BS8 1TQ, UK; Max Planck-Bristol Centre for Minimal Biology, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
  • Yoan Duhoo
    Protein Production and Structure Characterization Core Facility (PTPSP), School of Life Sciences, École polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Lars J Dornfeld
    Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Benjamin Dubreuil
    Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Sandrine Georgeon
    Laboratory of Protein Design and Immunoengineering, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Sergey Ovchinnikov
    Center for Systems Biology, Harvard University, Cambridge, MA 02138, United States.
  • Derek N Woolfson
    School of Chemistry, University of Bristol, Bristol BS8 1TS, UK; School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK; Bristol BioDesign Institute, University of Bristol, Life Sciences Building, Bristol BS8 1TQ, UK; Max Planck-Bristol Centre for Minimal Biology, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK. Electronic address: d.n.woolfson@bristol.ac.uk.
  • Bruno E Correia
    Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Sucharita Dey
    Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Rajasthan, India. Electronic address: sdey@iitj.ac.in.
  • Emmanuel D Levy
    Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: emmanuel.levy@gmail.com.

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