Aromatic-participant interactions are essential for disulfide-bond-based trimerization in human heat shock transcription factor 1.
Heat shock transcription factor 1 (HSF1) is a central regulator in the heat shock response. However, its trimerization mechanism remains unclear. Here, we demonstrate that three conserved aromatic amino acids (Trp37, Tyr60, and Phe104) are essential for HSF1 trimerization. Point mutation and fluorescence spectroscopy experiments show that an intramolecular interaction between Tyr60 and alpha-helix 1 in the DNA-binding domain stabilizes the HSF1 structure upon heat stress. Furthermore, intermolecular aromatic-aromatic interaction between the Trp37 and Phe104 supports the approach with the Cys36 and Cys103. Thus, the existence of two differential interactions facilitates the formation of intermolecular disulfide bonds, leading to the heat-induced HSF1 trimerization.
Lu
Ming
M
Department of Chemistry, Pusan National University, 609-735 Busan, South of Korea.
Lee
Yun-Ju
YJ
Park
Sung-Min
SM
Kang
Ho Sung
HS
Kang
Shin Won
SW
Kim
Suhkmann
S
Park
Jang-Su
JS