Asp-52 in combination with Asp-398 plays a critical role in ATP hydrolysis of chaperonin GroEL

J Biol Chem. 2014 Oct 24;289(43):30005-11. doi: 10.1074/jbc.M114.593822. Epub 2014 Sep 8.

Abstract

The Escherichia coli chaperonin GroEL is a double-ring chaperone that assists protein folding with the aid of GroES and ATP. Asp-398 in GroEL is known as one of the critical residues on ATP hydrolysis because GroEL(D398A) mutant is deficient in ATP hydrolysis (<2% of the wild type) but not in ATP binding. In the archaeal Group II chaperonin, another aspartate residue, Asp-52 in the corresponding E. coli GroEL, in addition to Asp-398 is also important for ATP hydrolysis. We investigated the role of Asp-52 in GroEL and found that ATPase activity of GroEL(D52A) and GroEL(D52A/D398A) mutants was ∼ 20% and <0.01% of wild-type GroEL, respectively, indicating that Asp-52 in E. coli GroEL is also involved in the ATP hydrolysis. GroEL(D52A/D398A) formed a symmetric football-shaped GroEL-GroES complex in the presence of ATP, again confirming the importance of the symmetric complex during the GroEL ATPase cycle. Notably, the symmetric complex of GroEL(D52A/D398A) was extremely stable, with a half-time of ∼ 150 h (∼ 6 days), providing a good model to characterize the football-shaped complex.

Keywords: ATPase; Chaperone; Chaperonin; GroEL; GroES; Protein Aggregation; Protein Folding; Protein Misfolding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Aspartic Acid / metabolism*
  • Binding Sites
  • Chaperonin 10 / metabolism
  • Chaperonin 10 / ultrastructure
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / metabolism*
  • Chaperonin 60 / ultrastructure
  • Escherichia coli / metabolism*
  • Hydrolysis
  • Malate Dehydrogenase / metabolism
  • Mutant Proteins / metabolism
  • Negative Staining
  • Protein Folding
  • Protein Stability
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Structure-Activity Relationship
  • Thiosulfate Sulfurtransferase / metabolism

Substances

  • Chaperonin 10
  • Chaperonin 60
  • Mutant Proteins
  • Protein Subunits
  • Aspartic Acid
  • Adenosine Triphosphate
  • Malate Dehydrogenase
  • Thiosulfate Sulfurtransferase