Loading...
Thumbnail Image
Publication

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
... show 6 more
Citations
Altmetric:
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 mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology.
Description
Date
2023-01-23
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Research
Research Projects
Organizational Units
Journal Issue
Keywords
Protein folding, Structural biology, Systems biology
Citation
Burke, D.F., Bryant, P., Barrio-Hernandez, I. et al. Towards a structurally resolved human protein interaction network. Nat Struct Mol Biol 30, 216–225 (2023). https://doi.org/10.1038/s41594-022-00910-8
Embedded videos