1. Allosteric differences dictate GroEL complementation of E. coli
- Author
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Jared Sivinski, Duc Ngo, Christopher J. Zerio, Andrew J. Ambrose, Edmond R. Watson, Lynn K. Kaneko, Marius M. Kostelic, Mckayla Stevens, Anne‐Marie Ray, Yangshin Park, Chunxiang Wu, Michael T. Marty, Quyen Q. Hoang, Donna D. Zhang, Gabriel C. Lander, Steven M. Johnson, and Eli Chapman
- Subjects
Escherichia coli Proteins ,Biochemistry ,Article ,Adenosine Diphosphate ,Protein Subunits ,Adenosine Triphosphate ,Allosteric Regulation ,Chaperonin 10 ,Escherichia coli ,Genetics ,Molecular Biology ,Allosteric Site ,Heat-Shock Proteins ,Biotechnology - Abstract
GroES/GroEL is the only bacterial chaperone essential under all conditions, making it a potential antibiotic target. Rationally targeting ESKAPE GroES/GroEL as an antibiotic strategy necessitates studying their structure and function. Herein, we outline the structural similarities between Escherichia coli and ESKAPE GroES/GroEL and identify significant differences in intra- and inter-ring cooperativity, required in the refolding cycle of client polypeptides. Previously, we observed that one-half of ESKAPE GroES/GroEL family members could not support cell viability when each was individually expressed in GroES/GroEL-deficient E. coli cells. Cell viability was found to be dependent on the allosteric compatibility between ESKAPE and E. coli subunits within mixed (E. coli and ESKAPE) tetradecameric GroEL complexes. Interestingly, differences in allostery did not necessarily result in differences in refolding rate for a given homotetradecameric chaperonin. Characterization of ESKAPE GroEL allostery, ATPase, and refolding rates in this study will serve to inform future studies focused on inhibitor design and mechanism of action studies.
- Published
- 2022
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