title: Structural and evolutionary versatility in protein complexes with uneven stoichiometry.
abstract: Proteins assemble into complexes with diverse quaternary structures. Although most heteromeric complexes of known structure have even stoichiometry, a significant minority have uneven stoichiometry--that is, differing numbers of each subunit type. To adopt this uneven stoichiometry, sequence-identical subunits must be asymmetric with respect to each other, forming different interactions within the complex. Here we first investigate the occurrence of uneven stoichiometry, demonstrating that it is common in vitro and is likely to be common in vivo. Next, we elucidate the structural determinants of uneven stoichiometry, identifying six different mechanisms by which it can be achieved. Finally, we study the frequency of uneven stoichiometry across evolution, observing a significant enrichment in bacteria compared with eukaryotes. We show that this arises due to a general increased tendency for bacterial proteins to self-assemble and form homomeric interactions, even within the context of a heteromeric complex.
authors.affiliation: 1] MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK [2] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Marsh
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Rees
authors.affiliation: Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Ahnert
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK [2] Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK [3] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D019295:Computational Biology; D003460:Crystallization; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D011506:Proteins