title: Protein complexes are under evolutionary selection to assemble via ordered pathways.
abstract: Is the order in which proteins assemble into complexes important for biological function? Here, we seek to address this by searching for evidence of evolutionary selection for ordered protein complex assembly. First, we experimentally characterize the assembly pathways of several heteromeric complexes and show that they can be simply predicted from their three-dimensional structures. Then, by mapping gene fusion events identified from fully sequenced genomes onto protein complex assembly pathways, we demonstrate evolutionary selection for conservation of assembly order. Furthermore, using structural and high-throughput interaction data, we show that fusion tends to optimize assembly by simplifying protein complex topologies. Finally, we observe protein structural constraints on the gene order of fusion that impact the potential for fusion to affect assembly. Together, these results reveal the intimate relationships among protein assembly, quaternary structure, and evolution and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways.
authors.affiliation: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Marsh
authors.forename: Helena
authors.initials: H
authors.lastname: Hernández
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hall
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Ahnert
authors.forename: Tina
authors.initials: T
authors.lastname: Perica
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D030562:Databases, Protein; D056890:Eukaryota / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D050939:Gene Fusion; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism*; D058105:Polymerization; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins