Co-evolution at protein-protein interfaces guides inference of stoichiometry of oligomeric protein complexes by de novo structure prediction

• Verfasst von: Kilian, Max [VerfasserIn]
• Verfasst von: Bischofs-Pfeifer, Ilka [VerfasserIn]
• Titel: Co-evolution at protein-protein interfaces guides inference of stoichiometry of oligomeric protein complexes by de novo structure prediction
• Verf.angabe: Max Kilian, Ilka B. Bischofs
• Jahr: 2023
• Umfang: 20 S.
• Illustrationen: Illustrationen
• Fussnoten: Vorab online veröffentlicht: 30. September 2023 ; Gesehen am 26.10.2023
• Titel Quelle: Enthalten in: Molecular microbiology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1987
• Jahr Quelle: 2023
• Band/Heft Quelle: 120(2023), 5, Seite 763-782
• ISSN Quelle: 1365-2958
• DOI: doi:10.1111/mmi.15169
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alphafold2
• Sach-SW: Bacillus subtilis
• Sach-SW: co-evolution analysis
• Sach-SW: protein complexes
• Sach-SW: spore germination
• K10plus-PPN: 1868116689

Abstract

The quaternary structure with specific stoichiometry is pivotal to the specific function of protein complexes. However, determining the structure of many protein complexes experimentally remains a major bottleneck. Structural bioinformatics approaches, such as the deep learning algorithm Alphafold2-multimer (AF2-multimer), leverage the co-evolution of amino acids and sequence-structure relationships for accurate de novo structure and contact prediction. Pseudo-likelihood maximization direct coupling analysis (plmDCA) has been used to detect co-evolving residue pairs by statistical modeling. Here, we provide evidence that combining both methods can be used for de novo prediction of the quaternary structure and stoichiometry of a protein complex. We achieve this by augmenting the existing AF2-multimer confidence metrics with an interpretable score to identify the complex with an optimal fraction of native contacts of co-evolving residue pairs at intermolecular interfaces. We use this strategy to predict the quaternary structure and non-trivial stoichiometries of Bacillus subtilis spore germination protein complexes with unknown structures. Co-evolution at intermolecular interfaces may therefore synergize with AI-based de novo quaternary structure prediction of structurally uncharacterized bacterial protein complexes.