Combining Natural Sequence Variation with High Throughput Mutational Data to Reveal Protein Interaction Sites

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The interactions of proteins with each other are essential for almost all biological processes. Many of the sites of protein contact have evolved to maintain these interactions, but use different sets of amino acid residues. As a result, the residues at a contact site in a protein from one species might not allow a protein interaction when they are tested in a second species. This property underlies the idea of inter-species complementation assays, which test the effect of replacing protein segments from one species by their equivalents from another species. However, this approach has been highly limited in the number of changes that could be analyzed in a single study. Here, we present a novel approach that combines a high-throughput analysis of mutations in a single protein with the set of natural sequences corresponding to evolutionarily divergent variants of this protein. This integration step allows us to map at high resolution both sites of inter-protein interaction as well as intra-protein interaction. Our approach can be used with proteins that have limited functional and structural data, and it can be applied to improve the performance of computational tools that use sequence homology to predict function.

Vyšlo v časopise: Combining Natural Sequence Variation with High Throughput Mutational Data to Reveal Protein Interaction Sites. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004918
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004918

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