Protein complexes are under evolutionary selection to assemble via ordered pathways

Joseph A Marsh, Helena Hernández, Zoe Hall, Sebastian E Ahnert, Tina Perica, Carol V Robinson, Sarah A Teichmann

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)461-70
Number of pages10
Issue number2
Publication statusPublished - 11 Apr 2013


  • Bacteria
  • Databases, Protein
  • Eukaryota
  • Evolution, Molecular
  • Gene Fusion
  • Mass Spectrometry
  • Metabolic Networks and Pathways
  • Multiprotein Complexes
  • Polymerization
  • Protein Structure, Quaternary
  • Proteins


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