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PDB-wide identification of physiological hetero-oligomeric assemblies based on conserved quaternary structure geometry

, Emmanuel D Levy
Published in Cell Press
PMID: 34520740
Volume: 29
Issue: 11
Pages: 1303 - 1311

An accurate understanding of biomolecular mechanisms and diseases requires information on protein qua-ternary structure (QS). A critical challenge in inferring QS information from crystallography data is distinguishing biological interfaces from fortuitous crystal-packing contacts. Here, we employ QS conservation across homologs to infer the biological relevance of hetero-oligomers. We compare the structures and compositions of hetero-oligomers, which allow us to annotate 7,810 complexes as physiologically relevant, 1,060 as likely errors, and 1,432 with comparative information on subunit stoichiometry and composition. Excluding immuno-globulins, these annotations encompass over 51% of hetero-oligomers in the PDB. We curate a dataset of577 hetero-oligomeric complexes to benchmark these annotations, which reveals an accuracy >94%. When homology information is not available, we compare QS across repositories (PDB, PISA, and EPPIC) to derive confidence estimates. This work provides high-quality annotations along with a large benchmark dataset of hetero-assemblies.

About the journal
PublisherCell Press
Open AccessYes