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

Tali Haviv Reingewertz, Miki Ben-Maimon, Zohar Zafrir, Tamir Tuller, Amnon Horovitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere5087
JournalProtein Science
Volume33
Issue number8
DOIs
StatePublished - Aug 2024

Funding

FundersFunder number
Minerva Foundation
US‐Israel Binational Science Foundation
United States-Israel Binational Science Foundation
Federal German Ministry for Education and Research2021077

    Keywords

    • GroEL
    • chaperonins
    • codon usage
    • protein folding
    • random mutagenesis

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