Crystal structure of the hexamer of human heat shock factor binding protein 1

Proteins. 2009 Apr;75(1):1-11. doi: 10.1002/prot.22216.


Heat shock response (HSR) is a ubiquitous cellular mechanism that copes with a variety of stresses. This response is mediated by a family of transcriptional activators, heat shock factors (HSFs), which are under tight regulation. HSF binding protein 1 (HSBP1) is a negative regulator of HSR and is reported to bind specifically with the active trimeric form of HSF1, thus inhibiting its activity. HSBP1 contains heptad-repeats in the primary sequence and was believed to stay in a trimer form in solution. We report the crystal structure of the trimerization domain of the M30I/L55P mutant of human HSBP1 at 1.8 A resolution. In this crystal form, the HSBP1 fragment of residues 6-53 forms a continuous, 11-turn long helix. The helix self-associates to form a parallel, symmetrical, triple coiled-coil helix bundle, which further assembles into a dimer of trimers in a head-to-head fashion. Solution study confirmed that the wild-type HSBP1 shares similar biophysical properties with the crystallized variant. Furthermore, we identified Ser31, which buried its polar side chain in the hydrophobic interior of the helix bundle, as a stability weak-spot. Substitution of this residue with Ile increases the melting temperature by 24 degrees C, implicating that this conserved serine residue is maintained at position 31 for functional purposes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Response
  • Humans
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Point Mutation
  • Protein Conformation
  • Protein Multimerization*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Transition Temperature


  • HSBP1 protein, human
  • Heat-Shock Proteins
  • Mutant Proteins
  • Recombinant Proteins