Structural insights into the specific binding of huntingtin proline-rich region with the SH3 and WW domains
Structural insights into the specific binding of huntingtin proline-rich region with the SH3 and WW domains
复制标题
DOI：
10.1016/j.str.2006.09.014
复制
发表时间：
2006-12-01
期刊：
影响因子：
5.7
通讯作者：
Hu, Hong-Yu
中科院分区：
文献类型：
--
作者：
Gao, Yong-Guang;Yan, Xian-Zhong;Hu, Hong-Yu
亨廷顿蛋白（Htt）与含有SH 3结构域或WW结构域的蛋白质的相互作用涉及亨廷顿病（HD）的发病机制。我们报道了Htt脯氨酸富集区（PRR）与SH 3GL 3-SH 3结构域和HYPA-WW 1 -2结构域对的特异性相互作用。结果表明，Htt PRR通过几乎整个链与SH 3结构域结合，并且结构域上的结合区域包括典型的PxxP结合位点和特异性口袋。PRR的C末端定向于特异性口袋，而N末端定向于PxxP结合位点。Htt PRR也可以特异性结合WW 1 -2; N-末端部分优先结合WW 1，而C-末端部分结合WW 2。这项研究提供了结构的见解，具体之间的相互作用Htt PRR和它的结合伙伴，以及改变这些相互作用，涉及PRR，这可能有影响的理解HD。
The interactions of huntingtin (Htt) with the SH3 domain-or WW domain-containing proteins have been implicated in the pathogenesis of Huntington's disease (HD). We report the specific interactions of Htt proline-rich region (PRR) with the SH3GL3-SH3 domain and HYPA-WW1-2 domain pair by NMR. The results show that Htt PRR binds with the SH3 domain through nearly its entire chain, and that the binding region on the domain includes the canonical PxxP-binding site and the specificity pocket. The C terminus of PRR orients to the specificity pocket, whereas the N terminus orients to the PxxP-binding site. Htt PRR can also specifically bind to WW1-2; the N-terminal portion preferentially binds to WW1, while the C-terminal portion binds to WW2. This study provides structural insights into the specific interactions between Htt PRR and its binding partners as well as the alteration of these interactions that involve PRR, which may have implications for the understanding of HD.