Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
FEBS J. 2010 Feb;277(4):1058-66. doi: 10.1111/j.1742-4658.2009.07549.x. Epub 2010 Jan 18.
Tetratricopeptide repeats (TPRs) are protein domains that mediate key protein-protein interactions in cells. Several TPR domains bind the C-termini of the chaperones heat shock protein (Hsp)90 and/or Hsp70, and exchange of such binding partners is key for the heat shock response. We have previously described the design of a TPR protein that binds tightly and specifically to the C-terminus of Hsp90, and in doing so, is able to inhibit chaperone function in vivo. Here we present the X-ray crystal structure of the designed TPR domain (CTPR390) in complex with its peptide ligand--the C-terminal residues of Hsp90 (peptide MEEVD). This structure reveals two interesting aspects of the TPR modules. First, a new packing arrangement of 3-TPR modules is observed. The TPR units stack against each other in an unusual fashion to form infinite superhelices in the crystal. Second, the structure provides insights into the molecular basis of TPR-ligand recognition.
四肽重复序列（TPR）是介导细胞中关键蛋白-蛋白相互作用的蛋白质结构域。几个 TPR 结构域结合伴侣热休克蛋白（Hsp）90 和/或 Hsp70 的 C 末端，这种结合伙伴的交换对于热休克反应至关重要。我们之前描述了一种 TPR 蛋白的设计，该蛋白与 Hsp90 的 C 末端紧密且特异性结合，并且能够在体内抑制伴侣功能。在这里，我们展示了设计的 TPR 结构域（CTPR390）与肽配体（Hsp90 的 C 末端残基肽 MEEVD）复合物的 X 射线晶体结构。该结构揭示了 TPR 模块的两个有趣方面。首先，观察到 3-TPR 模块的新包装排列。TPR 单元以不寻常的方式彼此堆叠，在晶体中形成无限的超螺旋。其次，该结构提供了 TPR-配体识别的分子基础的见解。
