Banting and Best Department of Medical Research, Donnelly Centre, 160 College Street, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Nature. 2012 Sep 27;489(7417):585-9. doi: 10.1038/nature11354. Epub 2012 Sep 2.
Macromolecular assemblies involving membrane proteins (MPs) serve vital biological roles and are prime drug targets in a variety of diseases. Large-scale affinity purification studies of soluble-protein complexes have been accomplished for diverse model organisms, but no global characterization of MP-complex membership has been described so far. Here we report a complete survey of 1,590 putative integral, peripheral and lipid-anchored MPs from Saccharomyces cerevisiae, which were affinity purified in the presence of non-denaturing detergents. The identities of the co-purifying proteins were determined by tandem mass spectrometry and subsequently used to derive a high-confidence physical interaction map encompassing 1,726 membrane protein-protein interactions and 501 putative heteromeric complexes associated with the various cellular membrane systems. Our analysis reveals unexpected physical associations underlying the membrane biology of eukaryotes and delineates the global topological landscape of the membrane interactome.
涉及膜蛋白 (MP) 的大分子组装体发挥着至关重要的生物学作用，是多种疾病的主要药物靶点。已经完成了多种模式生物的可溶性蛋白复合物的大规模亲和纯化研究，但迄今为止尚未描述 MPs 复合物成员的全面特征。在这里，我们报告了对酿酒酵母中 1590 种假定的完整、周边和脂锚定 MP 的完整调查，这些 MP 是在非变性洗涤剂存在下进行亲和纯化的。共纯化蛋白的身份通过串联质谱法确定，并随后用于得出一个包含 1726 个膜蛋白-蛋白相互作用和 501 个与各种细胞膜系统相关的假定异源复合物的高可信度物理相互作用图。我们的分析揭示了真核生物膜生物学的意外物理关联，并描绘了膜相互作用组的全局拓扑景观。
