Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand
Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand
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DOI：
10.1111/j.1742-4658.2009.07549.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.4
通讯作者：
Regan, Lynne
中科院分区：
文献类型：
--
作者：
Cortajarena, Aitziber L.;Wang, Jimin;Regan, Lynne
三肽重复序列（TPR）是介导细胞中关键蛋白质-蛋白质相互作用的蛋白质结构域。几个TPR结构域结合分子伴侣热休克蛋白（HSP）90和/或HSP 70的C-末端，并且这种结合伴侣的交换是热休克反应的关键。我们先前已经描述了TPR蛋白的设计，其紧密且特异性地结合到Hsp 90的C-末端，并且在这样做时，能够抑制体内伴侣蛋白功能。在这里，我们提出了X-射线晶体结构的设计TPR域（CTPR 390）与它的肽配体的复合物-C-末端残基的热休克蛋白90（肽MEEVD）。这个结构揭示了TPR模块的两个有趣的方面。首先，观察到一种新的3-TPR组件的包装安排。TPR单元以一种不寻常的方式相互堆叠，在晶体中形成无限的超螺旋。第二，结构提供了深入了解TPR-配体识别的分子基础。
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.