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TitleAn atlas of protein homo-oligomerization across domains of life.
Journal, issue, pagesCell, Vol. 187, Issue 4, Page 999-1010.e15, Year 2024
Publish dateFeb 15, 2024
AuthorsHugo Schweke / Martin Pacesa / Tal Levin / Casper A Goverde / Prasun Kumar / Yoan Duhoo / Lars J Dornfeld / Benjamin Dubreuil / Sandrine Georgeon / Sergey Ovchinnikov / Derek N Woolfson / Bruno E Correia / Sucharita Dey / Emmanuel D Levy /
PubMed AbstractProtein structures are essential to understanding cellular processes in molecular detail. While advances in artificial intelligence revealed the tertiary structure of proteins at scale, their ...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.
External linksCell / PubMed:38325366
MethodsEM (single particle) / X-ray diffraction
Resolution1.85 - 2.8 Å
Structure data

EMDB-17402, PDB-8p49:
Uncharacterized Q8U0N8 protein from Pyrococcus furiosus
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-18415, PDB-8qhp:
Cysteine tRNA ligase homodimer
Method: EM (single particle) / Resolution: 2.8 Å

PDB-8q70:
tRNA pseudouridine synthase A homodimer
Method: X-RAY DIFFRACTION / Resolution: 1.85 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-CL:
Unknown entry / Chloride

ChemComp-HOH:
WATER / Water

ChemComp-ZN:
Unknown entry

Source
  • pyrococcus furiosus dsm 3638 (archaea)
  • pyrococcus furiosus (archaea)
KeywordsUNKNOWN FUNCTION / uncharacterized / hexamer / pyrococcus / pore / ISOMERASE / pseudouridine / synthase / homodimer / tRNA / LIGASE / cysteine / synthetase / RNA

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