Towards a structurally resolved human protein interaction network

Burke, David F.; Bryant, Patrick; Barrio‐Hernandez, Inigo; Memon, Danish; Pozzati, Gabriele; Shenoy, Aditi; Zhu, Wensi; Dunham, Alistair S.; Albanese, Pascal; Keller, Andrew; Scheltema, Richard A.; Bruce, James E.; Leitner, Alexander; Kundrotas, Petras J.; Beltrão, Pedro; Elofsson, Arne

doi:10.1038/s41594-022-00910-8

articleNature Structural & Molecular BiologyJan 23, 2023HYBRID OA

Towards a structurally resolved human protein interaction network

DFDavid F. Burke PBPatrick Bryant IBInigo Barrio‐Hernandez DMDanish Memon GPGabriele Pozzati

European Bioinformatics Institute · Stockholm University · +8 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential…

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Topics

Keywords

Computational biology
Protein–protein interaction
Biology
Homology modeling
Human disease
Phosphorylation
Protein structure
Human cell

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