Integral membrane proteins: bottom-up, top-down and structural proteomics.
Integral membrane proteins: bottom-up, top-down and structural proteomics.
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DOI：
10.1080/14789450.2017.1359545
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发表时间：
2017-08
影响因子：
3.4
通讯作者：
Whitelegge JP
中科院分区：
文献类型：
--
作者：
Kar UK;Simonian M;Whitelegge JP
完整的膜蛋白和脂质构成包围细胞和亚细胞区室的双层膜，并调节它们之间的分子和信息的运动。由于膜蛋白药物靶点代表了蛋白质组中不成比例的大部分，因此需要及时审查技术发展。对Pubmed等公共资源进行了调查。自下而上的蛋白质组学分析现在允许有效的提取和消化，使得膜蛋白覆盖基本上是完整的，约占蛋白质组的三分之一。然而，这种覆盖依赖于亲水环区域，而跨膜结构域通常在基于肽的策略中覆盖较差。自上而下的质谱法，其中完整的膜蛋白在气相中被片段化，在跨膜区域提供了良好的覆盖率，膜组分产生高通量自上而下的蛋白质组学。膜蛋白复合物的天然质谱分析的令人兴奋的进展提供了对亚基化学计量和脂质结合的见解，并且交联策略正在贡献关键的体内信息。从文献中可以清楚地看出，膜蛋白的整合已经屈服于蛋白质化学和质谱的先进技术，其应用仅受研究人员想象力的限制。翻译到临床的关键进展强调。
Integral membrane proteins and lipids constitute the bilayer membranes that surround cells and sub-cellular compartments, and modulate movements of molecules and information between them. Since membrane protein drug targets represent a disproportionately large segment of the proteome, technical developments need timely review. Publically available resources such as Pubmed were surveyed. Bottom-up proteomics analyses now allow efficient extraction and digestion such that membrane protein coverage is essentially complete, making up around one third of the proteome. However, this coverage relies upon hydrophilic loop regions while transmembrane domains are generally poorly covered in peptide-based strategies. Top-down mass spectrometry where the intact membrane protein is fragmented in the gas phase gives good coverage in transmembrane regions, and membrane fractions are yielding to high-throughput top-down proteomics. Exciting progress in native mass spectrometry of membrane protein complexes is providing insights into subunit stoichiometry and lipid binding, and cross-linking strategies are contributing critical in-vivo information. It is clear from the literature that integral membrane proteins have yielded to advanced techniques in protein chemistry and mass spectrometry, with applications limited only by the imagination of investigators. Key advances toward translation to the clinic are emphasized.
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影响因子：
16.6
作者：
Christoforou A;Mulvey CM;Breckels LM;Geladaki A;Hurrell T;Hayward PC;Naake T;Gatto L;Viner R;Martinez Arias A;Lilley KS
通讯作者：
Lilley KS
影响因子：
4.4
作者：
Erde, Jonathan;Loo, Rachel R. Ogorzalek;Loo, Joseph A.
通讯作者：
Loo, Joseph A.
影响因子：
2.9
作者：
Carroll, Joe;Fearnley, Ian M.;Walker, John E.
通讯作者：
Walker, John E.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd