title: Alpha-helix 1 in the DNA-binding domain of heat shock factor 1 regulates its heat-induced trimerization and DNA-binding.
abstract: Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. The role of alpha-helix1 (H1) in its DNA-binding domain (DBD) during HSF1 activation remains unknown. Here, HSF1 lacking H1 loses its heat-induced activity, suggesting the importance of the latter. Furthermore, the CD spectra and AMBER prediction show that this H1 deficiency does not change the structure of HSF1 monomer, but does impact its heat-induced trimerization. Point mutation showed that Phe18 in H1 interacts with Tyr60, and that Trp23 interacts with Phe104 by an aromatic-aromatic interaction. Thus, the presence of H1 stabilizes the DBD structure, which facilitates the heat-induced trimerization and DNA-binding of HSF1.
authors.affiliation: Department of Chemistry, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Kwang-Jea
authors.initials: KJ
authors.lastname: Sohn
authors.forename: Si-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Chun-Ri
authors.initials: CR
authors.lastname: Li
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.forename: Dong-Kyoo
authors.initials: DK
authors.lastname: Kim
authors.forename: Jang-Su
authors.initials: JS
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D004247:DNA