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Protein binding and folding through an evolutionary lens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology, Biochemistry and Cancer.ORCID iD: 0000-0003-1516-7228
2025 (English)In: Current opinion in structural biology, ISSN 0959-440X, E-ISSN 1879-033X, Vol. 90, article id 102980Article, review/survey (Refereed) Published
Abstract [en]

Protein-protein associations are often mediated by an intrinsically disordered protein region interacting with a folded domain in a coupled binding and folding reaction. Classic physical organic chemistry approaches together with structural biology have shed light on mechanistic aspects of such reactions. Further insight into general principles may be obtained by interpreting the results through an evolutionary lens. This review attempts to provide an overview on how the analysis of binding and folding reactions can benefit from an evolutionary approach, and is aimed at protein scientists without a background in evolution. Evolution constantly reshapes existing proteins by sampling more or less fit variants. Most new variants are weeded out as generations and new species come and go over hundreds to hundreds of millions of years. The huge ongoing genome sequencing efforts have provided us with a snapshot of existing adapted fit-for-purpose protein homologs in thousands of different organisms. Comparison of present-day orthologs and paralogs highlights general principles of the evolution of coupled binding and folding reactions and demonstrate a great potential for evolution to operate on disordered regions and modulate affinity and specificity of the interactions.

Place, publisher, year, edition, pages
Elsevier, 2025. Vol. 90, article id 102980
National Category
Molecular Biology Biophysics
Identifiers
URN: urn:nbn:se:uu:diva-549505DOI: 10.1016/j.sbi.2024.102980ISI: 001399739700001PubMedID: 39817990Scopus ID: 2-s2.0-85214834163OAI: oai:DiVA.org:uu-549505DiVA, id: diva2:1939101
Funder
Swedish Research Council, 2020-04395Available from: 2025-02-20 Created: 2025-02-20 Last updated: 2025-02-20Bibliographically approved

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