An atlas of protein homo-oligomerization across domains of life
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.
WOS:001185149700001
2024-02-15
187
4
REVIEWED
Funder | Grant Number |
Peter und Traudl Engelhorn Stiftung | |
Biotechnology and Biological Sciences Research Council (BBSRC) | BB/R00661X/1 |
BrisSynBio | |
BBSRC/Engineering and Physical Sciences Research Council-funded Synthetic Biology Research Centre | BB/L01386X/1 |
Swiss National Science Foundation | |
NCCR in Chemical Biology | |
NCCR in Molecular Systems Engineering | |
Swiss Cancer League | KFS-5032-02-2020 |
European Research Council (ERC) under the European Union | 819318 |
HFSP | RGP0016/2022 |
Israel Science Foundation | 1452/18 |
Abisch-Frenkel Foundation | |
Amgen for this project | |
Department of Biotechnology, Govt. India | RLS: BT/RLF/Re-entry/10/2020 |