Crystal structure of yeast Sis1 peptide-binding fragment and Hsp70 Ssa1 C-terminal complex
Crystal structure of yeast Sis1 peptide-binding fragment and Hsp70 Ssa1 C-terminal complex
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DOI：
10.1042/bj20060618
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发表时间：
2006-09-15
影响因子：
4.1
通讯作者：
Sha, Bingdong
中科院分区：
文献类型：
--
作者：
Li, Jingzhi;Wu, Yunkun;Sha, Bingdong
热休克蛋白（Hsp）40促进Hsp 70在许多细胞过程中的关键作用，如蛋白质的折叠、组装、降解和体内易位。Hsp 40和Hsp 70紧密联系以实现这些不同的功能。热休克蛋白70中保守的C-末端EEVD基序已被证明通过未知的机制调节热休克蛋白40-热休克蛋白70的相互作用。在这里，我们通过确定与Hsp 70 Ssa 1 C-末端复合的酵母Hsp 40 Sis 1肽结合片段的晶体结构，为这种调节提供了结构基础。Ssa 1末端C端8个残基G（634）PTVEEVD（641）与Sis 1肽结合片段的结构域I形成β链。令人惊讶的是，Ssa 1 C-末端在Sis 1与非天然多肽相互作用的位点结合Sis 1。Ssa 1 C-末端EEVD基序内的带负电荷的残基与Sis 1中的带正电荷的残基形成广泛的电荷-电荷相互作用。基于结构的诱变数据支持结构观察结果。
Heat shock protein (Hsp) 40 facilitates the critical role of Hsp70 in a number of cellular processes such as protein folding, assembly, degradation and translocation in vivo. Hsp40 and Hsp70 stay in close contact to achieve these diverse functions. The conserved C-terminal EEVD motif in Hsp70 has been shown to regulate Hsp40-Hsp70 interaction by an unknown mechanism. Here, we provide a structural basis for this regulation by determining the crystal structure of yeast Hsp40 Sis1 peptide-binding fragment complexed with the Hsp70 Ssa1 C-terminal. The Ssa1 extreme C-terminal eight residues, G(634)PTVEEVD(641), form a beta-strand with the domain I of Sis1 peptide-binding fragment. Surprisingly, the Ssa1 C-terminal binds Sis1 at the site where Sis1 interacts with the non-native polypeptides. The negatively charged residues within the EEVD motif in Ssa1 C-terminal form extensive charge-charge interactions with the positively charged residues in Sis1. The structure-based mutagenesis data support the structural observations.