Allosteric differences dictate GroEL complementation of E. coli

FASEB J. 2022 Mar;36(3):e22198. doi: 10.1096/fj.202101708RR.


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.

Keywords: ESKAPE; GroEL; GroES; allostery; chaperone; chaperonin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Allosteric Site*
  • Chaperonin 10 / chemistry
  • Chaperonin 10 / genetics
  • Chaperonin 10 / metabolism
  • Escherichia coli
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism


  • Chaperonin 10
  • Escherichia coli Proteins
  • GroE protein, E coli
  • Heat-Shock Proteins
  • Protein Subunits
  • Adenosine Diphosphate
  • Adenosine Triphosphate