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Crystal structure of the hexamer of human heat shock factor binding protein 1
Author(s) -
Liu Xueqi,
Xu Lingfeng,
Liu Yiwei,
Tong Xiaohang,
Zhu Guangyu,
Zhang Xuejun C.,
Li Xuemei,
Rao Zihe
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22216
Subject(s) - random hexamer , trimer , helix bundle , heat shock factor , dimer , crystallography , heptad repeat , chemistry , mutant , coiled coil , biophysics , protein structure , stereochemistry , heat shock protein , peptide sequence , biology , biochemistry , hsp70 , gene , organic chemistry
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 Å 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°C, implicating that this conserved serine residue is maintained at position 31 for functional purposes. Proteins 2009. © 2008 Wiley‐Liss, Inc.