An interdomain sector mediating allostery in Hsp70 molecular chaperones

Robert G. Smock, Olivier Rivoire, William P. Russ, Joanna F. Swain, Stanislas Leibler, Rama Ranganathan, Lila M. Gierasch

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Allosteric coupling between protein domains is fundamental to many cellular processes. For example, Hsp70 molecular chaperones use ATP binding by their actin-like N-terminal ATPase domain to control substrate interactions in their C-terminal substrate-binding domain, a reaction that is critical for protein folding in cells. Here, we generalize the statistical coupling analysis to simultaneously evaluate co-evolution between protein residues and functional divergence between sequences in protein sub-families. Applying this method in the Hsp70/110 protein family, we identify a sparse but structurally contiguous group of co-evolving residues called a ĝ€ sectorĝ€™, which is an attribute of the allosteric Hsp70 sub-family that links the functional sites of the two domains across a specific interdomain interface. Mutagenesis of Escherichia coli DnaK supports the conclusion that this interdomain sector underlies the allosteric coupling in this protein family. The identification of the Hsp70 sector provides a basis for further experiments to understand the mechanism of allostery and introduces the idea that cooperativity between interacting proteins or protein domains can be mediated by shared sectors.

Original languageEnglish (US)
Article number414
JournalMolecular Systems Biology
Volume6
DOIs
StatePublished - Oct 6 2010

    Fingerprint

Keywords

  • SCA
  • allostery
  • chaperone
  • co-evolution
  • sector

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Smock, R. G., Rivoire, O., Russ, W. P., Swain, J. F., Leibler, S., Ranganathan, R., & Gierasch, L. M. (2010). An interdomain sector mediating allostery in Hsp70 molecular chaperones. Molecular Systems Biology, 6, [414]. https://doi.org/10.1038/msb.2010.65