Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90
Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90
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DOI：
10.1074/jbc.m111.287458
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发表时间：
2012-02-17
影响因子：
4.8
通讯作者：
Houry, Walid A.
中科院分区：
文献类型：
--
作者：
Jimenez, Beatriz;Ugwu, Francisca;Houry, Walid A.
Tah 1和Pih 1是新的Hsp 90相互作用子。Tah 1作为Hsp 90的辅因子来稳定Pih 1。在酵母中，发现Hsp 90、Tah 1和Pih 1形成一种复合物，该复合物通过它们对盒C/D小核仁核糖核蛋白组装的作用而为核糖体RNA加工所需。Tah 1是一个最小的111个氨基酸残基的三肽重复蛋白，结合到热休克蛋白90分子伴侣的C末端，而Pih 1由未知折叠的344个残基组成。Tah 1的NMR结构已被解析，该结构显示存在两个tetratricopeptide重复基序，随后是C螺旋和非结构化区域。Tah 1与Hsp 90的结合是由Hsp 90的EEVD C-末端残基介导的，其与Tah 1形成的带正电荷的通道结合。Tah 1中也存在5个高度保守的残基，它们形成与结合肽的最终Asp-0残基紧密相互作用的双羧酸钳。Tah 1通过C螺旋和非结构化区域与Pih 1的C末端结合。Pih 1的C末端在体外和体内使蛋白质不稳定，而Tah 1与Pih 1的结合允许形成稳定的复合物。基于我们的数据，提出了一个模型的热休克蛋白90-Tah 1-Pih 1三元复合物。
Tah1 and Pih1 are novel Hsp90 interactors. Tah1 acts as a cofactor of Hsp90 to stabilize Pih1. In yeast, Hsp90, Tah1, and Pih1 were found to form a complex that is required for ribosomal RNA processing through their effect on box C/D small nucleolar ribonucleoprotein assembly. Tah1 is a minimal tetratricopeptide repeat protein of 111 amino acid residues that binds to the C terminus of the Hsp90 molecular chaperone, whereas Pih1 consists of 344 residues of unknown fold. The NMR structure of Tah1 has been solved, and this structure shows the presence of two tetratricopeptide repeat motifs followed by a C helix and an unstructured region. The binding of Tah1 to Hsp90 is mediated by the EEVD C-terminal residues of Hsp90, which bind to a positively charged channel formed by Tah1. Five highly conserved residues, which form a two-carboxylate clamp that tightly interacts with the ultimate Asp-0 residue of the bound peptide, are also present in Tah1. Tah1 was found to bind to the C terminus of Pih1 through the C helix and the unstructured region. The C terminus of Pih1 destabilizes the protein in vitro and in vivo, whereas the binding of Tah1 to Pih1 allows for the formation of a stable complex. Based on our data, a model for an Hsp90-Tah1-Pih1 ternary complex is proposed.