The Molecular Basis of the Interaction of Cyclophilin?A with α‐Synuclein

摘要

Abstract > Peptidylprolyl isomerases (PPIases) catalyze cis/trans isomerization of prolines. The PPIase CypA colocalizes with the Parkinson's disease (PD)‐associated protein α‐synuclein in cells and interacts with α‐synuclein oligomers. Herein, we describe atomic insights into the molecular details of the α‐synuclein/CypA interaction. NMR spectroscopy shows that CypA catalyzes isomerization of proline?128 in the C‐terminal domain of α‐synuclein. Strikingly, we reveal a second CypA‐binding site formed by the hydrophobic sequence 47 GVVHGVATVA 56 , termed PreNAC. The 1.38?? crystal structure of the CypA/PreNAC complex displays a contact between alanine?53 of α‐synuclein and glutamine?111 in the catalytic pocket of CypA. Mutation of alanine?53 to glutamate, as found in patients with early‐onset PD, weakens the interaction of α‐synuclein with CypA. Our study provides high‐resolution insights into the structure of the PD‐associated protein α‐synuclein in complex with the most abundant cellular cyclophilin. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 肽基脯氨酰异构酶（pPiases）催化脯氨酸的顺式/反式异构化。 PPIASE CYPA与帕金森病（Pd） - 分配的蛋白质α-突触核蛋蛋白在细胞中分开并与α-突触核蛋白寡聚体相互作用。在此，我们描述了α-突触核蛋白/ CYPA相互作用的分子细节的原子洞察。 NMR光谱表明CYPA催化α-突触核蛋白的C-末端结构域的脯氨酸α128的异构化。令人惊讶的是，我们揭示了由疏水序列形成的第二个Cypa结合位点 47 </ sup> Gvvhgvatva. 56 </ sup> ，被称为prenac。 1.38 ?? Cypa / prenac复合物的晶体结构显示α-突触核蛋白和谷氨酰胺α111的丙氨酸α53之间的接触，Cypa的催化袋中。丙氨酸α53至谷氨酸的突变，如早期发作PD的患者中发现，削弱了α-突触核蛋白与CYPA的相互作用。我们的研究提供了与最丰富的细胞环旋蛋白复合物的PD相关蛋白α-突触核蛋白的结构高分辨率见解。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第14期</span><b style="margin: 0 2px;">|</b><span>共4页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cyclophilin&option=203" rel="nofollow">cyclophilin;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Parkinson's disease&option=203" rel="nofollow">Parkinson's disease;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=proline isomerization&option=203" rel="nofollow">proline isomerization;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=protein structure&option=203" rel="nofollow">protein structure;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=α-synuclein&option=203" rel="nofollow">α-synuclein;</a> </p> <div class="translation"> 机译：细胞苷;帕金森病;脯氨酸异构化;蛋白质结构;α-突触核蛋白; 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