芳香族参与相互作用对于人类热休克转录因子1中基于二硫键的三聚化至关重要。

Aromatic-participant interactions are essential for disulfide-bond-based trimerization in human heat shock transcription factor 1.

作者信息

Lu Ming, Lee Yun-Ju, Park Sung-Min, Kang Ho Sung, Kang Shin Won, Kim Suhkmann, Park Jang-Su

机构信息

Department of Chemistry, Pusan National University, 609-735 Busan, South of Korea.

出版信息

Biochemistry. 2009 May 12;48(18):3795-7. doi: 10.1021/bi802255c.

DOI:10.1021/bi802255c

PMID:19338268

Abstract

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.

摘要

热休克转录因子1（HSF1）是热休克反应中的核心调节因子。然而，其三聚化机制仍不清楚。在此，我们证明三个保守的芳香族氨基酸（Trp37、Tyr60和Phe104）对HSF1三聚化至关重要。点突变和荧光光谱实验表明，DNA结合结构域中Tyr60与α-螺旋1之间的分子内相互作用在热应激时稳定了HSF1结构。此外，Trp37和Phe104之间的分子间芳香-芳香相互作用支持了与Cys36和Cys103的接近。因此，两种不同相互作用的存在促进了分子间二硫键的形成，导致热诱导的HSF1三聚化。