Synonymous and non-synonymous codon substitutions can alleviate dependence on GroEL for folding.

Autor: Reingewertz TH; Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Ben-Maimon M; Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Zafrir Z; Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel., Tuller T; Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel.; The Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel., Horovitz A; Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2024 Aug; Vol. 33 (8), pp. e5087.
DOI: 10.1002/pro.5087
Abstrakt: The Escherichia coli GroEL/ES chaperonin system facilitates protein folding in an ATP-driven manner. There are <100 obligate clients of this system in E. coli although GroEL can interact and assist the folding of a multitude of proteins in vitro. It has remained unclear, however, which features distinguish obligate clients from all the other proteins in an E. coli cell. To address this question, we established a system for selecting mutations in mouse dihydrofolate reductase (mDHFR), a GroEL interactor, that diminish its dependence on GroEL for folding. Strikingly, both synonymous and non-synonymous codon substitutions were found to reduce mDHFR's dependence on GroEL. The non-synonymous substitutions increase the rate of spontaneous folding whereas computational analysis indicates that the synonymous substitutions appear to affect translation rates at specific sites.
(© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)
Databáze: MEDLINE
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