Large-scale discovery of protein interactions at residue resolution using co-evolution calculated from genomic sequences
By Anna G. Green, Hadeer Elhabashy, Kelly P. Brock, Rohan Maddamsetti, Oliver Kohlbacher, Debora Marks. 2021
103 citations recorded by the source corpus.
Increasing numbers of protein interactions have been identified in high-throughput experiments, but only a small proportion have solved structures. Recently, sequence coevolution-based approaches have led to a breakthrough in predicting monomer protein structures and protein interaction interfaces. Here, we address the challenges of large-scale interaction prediction at residue resolution with a fast alignment concatenation method and a probabilistic score for the interaction of residues. Importantly, this method (EVcomplex2) is able to assess the likelihood of a protein interaction, as we show here applied to large-scale experimental datasets where the pairwise interactions are unknown. We predict 504 interactions de novo in the E. coli membrane proteome, including 243 that are newly discovered. While EVcomplex2 does not require available structures, coevolving residue pairs can be used to produce structural models of protein interactions, as done here for membrane complexes including the Flagellar Hook-Filament Junction and the Tol/Pal complex. Our understanding of the residue-level details of protein interactions remains incomplete. Here, the authors show sequence coevolution can be used to infer interacting proteins with residue-level details, including predicting 467 interactions de novo in the Escherichia coli cell envelope proteome.
Subfields: Molecular Biology
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In Molecular Biology
- Gabriele Pozzati
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- Patrick Bryant
- Petras J. Kundrotas
- A. Leitner
- Pedro Beltrão
- Yi Zhao
- Zhenyu Yang
Citations in the corpus
- AlphaFold2 and its applications in the fields of biology and medicine (2023, background): “143 Yin et al. 144 examined the performance of AF2 in predicting structures of protein complexes from amino acid sequence.”
- Towards a structurally resolved human protein interaction network (2021, background): “The N-terminal domain in HNRNPC (16-85) is predicted to interact with the N-terminal domain of RALY (1-100).”
- Computed structures of core eukaryotic protein complexes (2021, unknown): “…ortholog sequences of the two proteins in many different species, joining them to create paired multiple sequence alignments (pMSAs), and then determining the extent to which changes in the sequences of orthologs for the first protein covary with ortholog sequence changes for the second ( 9 , 10 ).”