Substrate recognition of molecular chaperones

The Hsp90 chaperone consists of three domains. It dimerises via its C-terminus. Crystal structures were solved for all of its subdomains and in case of the E. coli homologue HtpG even the structure of the entire Hsp90 dimer. However, no substrate binding site could be discovered to date. Regions in all subdomains were proposed as substrate binding domains, so that the situation is very unclear.

We are working on mapping the substrate binding site. We have established segmental isotope labelling in our laboratory, which is in combination with NMR spectroscopy a very powerful tool. We also use the excellent mass spectrometry of the proteomics facility in Utrecht to determine the stoichiometry of substrate complexes and to characterise protein interaction surfaces.

• Molecular mechanisms of chaperone interaction with their substrates.
  - Substrate recognition of molecular chaperones
  - Mechanisms of chaperone-assisted protein folding
  - Structural properties of chaperone substrates

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