Single-spanning transmembrane domains in cell growth and cell-cell interactions More than meets the eye?
Single-spanning transmembrane domains in cell growth and cell-cell interactions More than meets the eye?
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DOI：
10.4161/cam.4.2.12430
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发表时间：
2010-04-01
影响因子：
3.2
通讯作者：
Sturgis, James
中科院分区：
文献类型：
--
作者：
Hubert, Pierre;Sawma, Paul;Sturgis, James
作为一个整体，完整的膜蛋白代表了约三分之一的测序基因组，超过50%的目前可用的药物靶向膜蛋白，通常是细胞表面受体。一些膜蛋白类，具有一定数量的跨膜（TM）螺旋，正受到人们的关注，因为它们的巨大的功能和药理学的重要性，如G蛋白偶联受体具有7个TM段。虽然它们代表了大约一半的所有膜蛋白，双位蛋白（只有1个TM螺旋）到目前为止还没有得到很好的表征。尽管它们包括许多必需的受体家族，例如粘附分子和受体酪氨酸激酶，但其中许多是生物药物（肽、抗体等）的极好靶点。越来越多的证据表明，这些受体的TM结构域之间的相互作用在信号传导中发挥着重要作用，通过同源和异源的协会，构象变化，组装的信号平台等显着，在单一结构域的突变是频繁的人类疾病，如癌症或发育障碍。这篇综述试图给出一个概述，目前的知识，这些相互作用，从结构数据到治疗的角度来看，专注于参与细胞信号的双位蛋白。
As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.