Discovery of novel membrane binding structures and functions.
Discovery of novel membrane binding structures and functions.
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DOI：
10.1139/bcb-2014-0074
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Overduin M
中科院分区：
文献类型：
--
作者：
Kufareva I;Lenoir M;Dancea F;Sridhar P;Raush E;Bissig C;Gruenberg J;Abagyan R;Overduin M
蛋白质的功能由其在亚细胞分布背景下的内在活性决定。膜将蛋白质定位在细胞区室中并控制它们的特异性活动。发现这种膜蛋白相互作用对于理解生物学机制非常重要，并且可以发现新的治疗干预位点。在这里，我们提出了一种检测膜相互作用蛋白质及其暴露的残基插入到脂质双层的方法。尽管开发过程涉及分析C1b、C2、ENTH、FYVE、Gla、普列克底物蛋白同源性（PH）和PX结构域如何结合膜，但所得的膜最佳对接面积（MODA）方法产生已知三维结构的给定蛋白质的预测，而不参考典型的膜靶向模块。该方法在Arf 1 GT3、ATF 2乙酰转移酶、von Willebrand因子A3结构域和淋病奈瑟菌MsrB蛋白上进行了测试，并分别用膜相互作用和非相互作用的FAPP 1和PKD 1普列克底物蛋白同源结构域进一步细化。此外，我们演示了如何使用这个工具来发现前所未有的膜结合功能所示的Bro1结构域的阿利克斯，这是发现识别lysobisphosphatidic酸（LBPA）。新的膜蛋白相互作用的验证依赖于其他技术，如核磁共振光谱（NMR），这是用来映射胶束相互作用的网站。总之，这表明，全基因组识别已知的和新的膜相互作用的蛋白质和网站现在是可行的，并提供了一个新的工具，功能注释的蛋白质组。
The function of a protein is determined by its intrinsic activity in the context of its subcellular distribution. Membranes localize proteins within cellular compartments and govern their specific activities. Discovering such membrane-protein interactions is important for understanding biological mechanisms, and could uncover novel sites for therapeutic intervention. Here we present a method for detecting membrane interactive proteins and their exposed residues that insert into lipid bilayers. Although the development process involved analysis of how C1b, C2, ENTH, FYVE, Gla, pleckstrin homology (PH) and PX domains bind membranes, the resulting Membrane Optimal Docking Area (MODA) method yields predictions for a given protein of known three dimensional structures without referring to canonical membrane-targeting modules. This approach was tested on the Arf1 GTPase, ATF2 acetyltransferase, von Willebrand factor A3 domain and Neisseria gonorrhoeae MsrB protein, and further refined with membrane interactive and non-interactive FAPP1 and PKD1 pleckstrin homology domains, respectively. Furthermore we demonstrate how this tool can be used to discover unprecedented membrane binding functions as illustrated by the Bro1 domain of Alix, which was revealed to recognize lysobisphosphatidic acid (LBPA). Validation of novel membrane-protein interactions relies on other techniques such as nuclear magnetic resonance spectroscopy (NMR) which was used here to map the sites of micelle interaction. Together this indicates that genome-wide identification of known and novel membrane interactive proteins and sites is now feasible, and provides a new tool for functional annotation of the proteome.
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影响因子：
8
作者：
Cheng, Y;Sequeira, SM;Patel, DJ
通讯作者：
Patel, DJ
影响因子：
64.5
作者：
Dessen, A;Tang, J;Somers, WS
通讯作者：
Somers, WS
影响因子：
2.9
作者：
Bollinger, JG;Diraviyam, K;Gelb, MH
通讯作者：
Gelb, MH
影响因子：
2.9
作者：
Kohout, SC;Corbalán-García, S;Falke, JJ
通讯作者：
Falke, JJ
影响因子：
64.8
作者：
Ford, MGJ;Mills, IG;McMahon, HT
通讯作者：
McMahon, HT