Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Cell. 2012 Aug 31;150(5):1068-81. doi: 10.1016/j.cell.2012.08.011.
Cellular processes often depend on stable physical associations between proteins. Despite recent progress, knowledge of the composition of human protein complexes remains limited. To close this gap, we applied an integrative global proteomic profiling approach, based on chromatographic separation of cultured human cell extracts into more than one thousand biochemical fractions that were subsequently analyzed by quantitative tandem mass spectrometry, to systematically identify a network of 13,993 high-confidence physical interactions among 3,006 stably associated soluble human proteins. Most of the 622 putative protein complexes we report are linked to core biological processes and encompass both candidate disease genes and unannotated proteins to inform on mechanism. Strikingly, whereas larger multiprotein assemblies tend to be more extensively annotated and evolutionarily conserved, human protein complexes with five or fewer subunits are far more likely to be functionally unannotated or restricted to vertebrates, suggesting more recent functional innovations.
细胞过程通常依赖于蛋白质之间稳定的物理联系。尽管最近取得了进展，但人类蛋白质复合物的组成知识仍然有限。为了弥补这一差距，我们应用了一种整合的全局蛋白质组学分析方法，基于培养的人细胞提取物的色谱分离，将其分成一千多个生化馏分，然后通过定量串联质谱进行分析，系统地鉴定了 3006 种稳定相关可溶性人类蛋白质之间的 13993 个高可信度物理相互作用网络。我们报告的 622 个假定蛋白质复合物中的大多数与核心生物过程有关，并包含候选疾病基因和未注释的蛋白质，以提供有关机制的信息。引人注目的是，尽管较大的多蛋白组装往往具有更广泛的注释和进化保守性，但具有五个或更少亚基的人类蛋白质复合物更有可能在功能上未注释或仅限于脊椎动物，这表明了更近期的功能创新。
