A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins

Bolla Jani Reddy; Corey Robin A.; Sahin Cagla; Gault Joseph; Hummer Alissa; Hopper Jonathan T. S.; Lane David P.; Drew David; Allison Timothy M.; Stansfeld Phillip J.; Robinson Carol V.; Landreh Michael

摘要

Abstract > Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non‐specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid‐binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent‐resistant lipids bound at the dimer interface in the leucine transporter show decreased k <sub>off</sub> rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid‐II results in the formation of a 1:1 protein–lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non‐annular lipids based on their exchange rates in solution. </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> > 膜蛋白与周围脂质的各种触点接合，但区分特异性结合的脂质和非特异性环形相互作用是一个具有挑战性的问题。利用不同脂质结合性能施加天然质谱至三个膜蛋白复合物，我们探讨洗涤剂与不同环境中结合的脂质竞争的能力。我们表明，预原素同源物蛋白酶上的环形位置的脂质可能与洗涤剂恒定交换。相反，在亮氨酸转运蛋白中的二聚体界面中结合的洗涤剂抗性脂质展示下降k <sub>关闭</ sub> 分子动力学模拟的速率。转向脂质絮凝酶Murj，我们发现添加天然底物脂质-II的添加导致形成1：1蛋白 - 脂质复合物，其中脂质不能通过从高度保护的活性位点移位。总之，我们基于溶液中的汇率区分非环状脂质。 </ 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9期</span><b style="margin: 0 2px;">|</b><span>共6页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bolla Jani Reddy&option=202" target="_blank" rel="nofollow">Bolla Jani Reddy;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Corey Robin A.&option=202" target="_blank" rel="nofollow">Corey Robin A.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sahin Cagla&option=202" target="_blank" rel="nofollow">Sahin Cagla;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gault Joseph&option=202" target="_blank" rel="nofollow">Gault Joseph;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hummer Alissa&option=202" target="_blank" rel="nofollow">Hummer Alissa;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hopper Jonathan T. S.&option=202" target="_blank" rel="nofollow">Hopper Jonathan T. S.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Lane David P.&option=202" target="_blank" rel="nofollow">Lane David P.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Drew David&option=202" target="_blank" rel="nofollow">Drew David;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Allison Timothy M.&option=202" target="_blank" rel="nofollow">Allison Timothy M.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Stansfeld Phillip J.&option=202" target="_blank" rel="nofollow">Stansfeld Phillip J.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Robinson Carol V.&option=202" target="_blank" rel="nofollow">Robinson Carol V.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Landreh Michael&option=202" target="_blank" rel="nofollow">Landreh Michael;</a> </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"> <p>Department of ChemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QZ UK;</p> <p>Department of BiochemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QU UK;</p> <p>Department of Microbiology Tumor and Cell BiologyKarolinska Institutet17165 Solna Sweden;</p> <p>Department of ChemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QZ UK;</p> <p>Department of BiochemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QU UK;</p> <p>OMass TherapeuticsThe Oxford Science Park The Schr?dinger Building Kidlington OX4 4GE UK;</p> <p>Department of Microbiology Tumor and Cell BiologyKarolinska Institutet17165 Solna Sweden;</p> <p>Department of Biochemistry and BiophysicsStockholm University10691 Stockholm Sweden;</p> <p>Biomolecular Interaction Centre and School of Physical and Chemical SciencesUniversity of CanterburyChristchurch 8140 New Zealand;</p> <p>Department of BiochemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QU UK;</p> <p>Department of ChemistryUniversity of OxfordSouth Parks Road Oxford OX1 3QZ UK;</p> <p>Department of Microbiology Tumor and Cell BiologyKarolinska Institutet17165 Solna Sweden;</p> </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=lipid binding&option=203" rel="nofollow">lipid binding;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=membrane protein structure&option=203" rel="nofollow">membrane protein structure;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=molecular dynamics&option=203" rel="nofollow">molecular dynamics;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=native mass spectrometry&option=203" rel="nofollow">native mass spectrometry;</a> </p> <div class="translation"> 机译：脂质结合;膜蛋白质结构;分子动力学;天然质谱; 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