Structural and evolutionary versatility in protein complexes with uneven stoichiometry

Nature Communications
Joseph A MarshSarah A Teichmann

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.

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Citations

Jan 26, 2016·Cell Reports·Jonathan N WellsJoseph A Marsh
Mar 27, 2016·Journal of Molecular Biology·Nicholas J FraserColin J Jackson
Apr 23, 2019·PLoS Computational Biology·Spencer E BlivenPhilip E Bourne
Jun 4, 2019·PLoS Computational Biology·Alexander S Leonard, Sebastian E Ahnert
Nov 29, 2015·Biochemical Society Transactions·Jonathan N WellsJoseph A Marsh
Dec 15, 2015·Science·Sebastian E AhnertSarah A Teichmann
May 21, 2020·Scientific Reports·Maayan Bonjack, David Avnir
May 1, 2018·PLoS Computational Biology·Spencer BlivenJose M Duarte
Jul 12, 2017·Scientific Reports·L Therese Bergendahl, Joseph A Marsh
Jun 18, 2017·Biochemical Society Transactions·Gábor Maksay, Joseph A Marsh
Mar 8, 2021·Nucleic Acids Research·Birgit H M MeldalPablo Porras
Feb 28, 2020·Cell Systems·James Christopher TaggartErik McShane
Jun 3, 2021·International Journal of Molecular Sciences·Patricia Alvarez-SieiroBert Poolman
Aug 28, 2021·International Journal of Molecular Sciences·Aljaž Gaber, Miha Pavšič

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