A structural model for GroEL-polypeptide recognition

Ashley M. Buckle, Ralph Zahn, Alan R. Fersht

Research output: Contribution to journalArticleResearchpeer-review

192 Citations (Scopus)

Abstract

A monomeric peptide fragment of GroEL, consisting of residues 191-376, is a mini-chaperone with a functional chaperoning activity. We have solved the crystal structure at 1.7 Å resolution of GroEL(191-376) with a 17- residue N-terminal tag. The N-terminal tag of one molecule binds in the active site of a neighboring molecule in the crystal. This appears to mimic the binding of a peptide substrate molecule. Seven substrate residues are bound in a relatively extended conformation. Interactions between the substrate and the active site are predominantly hydrophobic, but there are also four hydrogen bonds between the main chain of the substrate and side chains of the active site. Although the preferred conformation of a bound substrate is essentially extended, the flexibility of the active site may allow it to accommodate the binding of exposed hydrophobic surfaces in general, such as molten globule-type structures. GroEL can therefore help unfold proteins by binding to a hydrophobic region and exert a binding pressure toward the fully unfolded state, thus acting as an 'unfoldase.' The structure of the mini-chaperone is very similar to that of residues 191-376 in intact GroEL, so we can build it into GroEL and reconstruct how a peptide can bind to the tetradecamer. A ring of connected binding sites is noted that can explain many aspects of substrate binding and activity.

Original languageEnglish
Pages (from-to)3571-3575
Number of pages5
JournalProceedings of the National Academy of Sciences
Volume94
Issue number8
DOIs
Publication statusPublished - 15 Apr 1997
Externally publishedYes

Keywords

  • cpn60
  • crystallography
  • hsp60
  • mini-chaperone
  • protein folding

Cite this

Buckle, Ashley M. ; Zahn, Ralph ; Fersht, Alan R. / A structural model for GroEL-polypeptide recognition. In: Proceedings of the National Academy of Sciences. 1997 ; Vol. 94, No. 8. pp. 3571-3575.
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A structural model for GroEL-polypeptide recognition. / Buckle, Ashley M.; Zahn, Ralph; Fersht, Alan R.

In: Proceedings of the National Academy of Sciences, Vol. 94, No. 8, 15.04.1997, p. 3571-3575.

Research output: Contribution to journalArticleResearchpeer-review

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