An atlas of protein homo-oligomerization across domains of life

Schweke, H.; Levin, T.; Pacesa, M.; Goverde, C. A.; Kumar, P.; Duhoo, Y.; Dornfeld, L. J.; Dubreuil, B.; Georgeon, S.; Ovchinnikov, S.; Woolfson, D. N.; Correia, B. E.; Dey, S.; Levy, E. D.

doi:10.1101/2023.06.09.544317

bioRxiv · 10.1101/2023.06.09.544317

An atlas of protein homo-oligomerization across domains of life

Schweke, H.·Levin, T.·Pacesa, M.·Goverde, C. A.·Kumar, P.·Duhoo, Y.·Dornfeld, L. J.·Dubreuil, B.·Georgeon, S.·Ovchinnikov, S.·Woolfson, D. N.·Correia, B. E.·Dey, S.·Levy, E. D.

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Abstract

Protein structures are essential to understand cellular processes in molecular detail. While advances in AI revealed the tertiary structure of proteins at scale, their quaternary structure remains mostly unknown. Here, we describe a scalable strategy based on AlphaFold2 to predict homo-oligomeric assemblies across four proteomes spanning the tree of life. We find that 50% of archaeal, 45% of bacterial, and 20% of eukaryotic proteomes form homomers. Our predictions accurately capture protein homo-oligomerization, recapitulate megadalton complexes, and unveil hundreds of novel homo-oligomer types. Analyzing these datasets reveals coiled-coil regions as major enablers of quaternary structure evolution in Eukaryotes. Integrating these structures with omics data shows that a majority of known protein complexes are symmetric. Finally, these datasets provide a structural context for interpreting disease mutations, which we find enriched at interfaces. Our strategy is applicable to any organism and provides a comprehensive view of homo-oligomerization in proteomes, protein networks, and disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/544317v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@1507a12org.highwire.dtl.DTLVardef@7e522aorg.highwire.dtl.DTLVardef@1445410org.highwire.dtl.DTLVardef@eb09f7_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Schweke, H., Levin, T., Pacesa, M., Goverde, C. A., Kumar, P., Duhoo, Y., Dornfeld, L. J., Dubreuil, B., Georgeon, S., Ovchinnikov, S., Woolfson, D. N., Correia, B. E., Dey, S., Levy, E. D.. 2023-06-11. An atlas of protein homo-oligomerization across domains of life. https://doi.org/10.1101/2023.06.09.544317

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