The BioPlex Network: A Systematic Exploration of the Human Interactome.
The BioPlex Network: A Systematic Exploration of the Human Interactome.
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DOI：
10.1016/j.cell.2015.06.043
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发表时间：
2015-07-16
期刊：
影响因子：
64.5
通讯作者：
Gygi SP
中科院分区：
文献类型：
--
作者：
Huttlin EL;Ting L;Bruckner RJ;Gebreab F;Gygi MP;Szpyt J;Tam S;Zarraga G;Colby G;Baltier K;Dong R;Guarani V;Vaites LP;Ordureau A;Rad R;Erickson BK;Wühr M;Chick J;Zhai B;Kolippakkam D;Mintseris J;Obar RA;Harris T;Artavanis-Tsakonas S;Sowa ME;De Camilli P;Paulo JA;Harper JW;Gygi SP
蛋白质相互作用形成了一个网络，其结构驱动细胞功能，其组织为生物研究提供信息。利用高通量亲和纯化质谱仪，我们在HEK293T细胞中鉴定了2,594个人类蛋白的相互作用伙伴。由此产生的网络(BioPlex)包含7,668种蛋白质之间的23,744种相互作用，其中86%以前没有文献记载。BioPlex准确地描述了已知的复合体，对大多数Corum复合体的覆盖率达到80%-100%。该网络很容易细分成与功能相关蛋白质的复合体或簇相对应的群落。更广泛地说，网络结构反映了细胞定位、生物过程和分子功能，使数千种蛋白质的功能表征成为可能。网络结构还揭示了数千个蛋白质结构域之间的联系，为研究结构相关的蛋白质提供了基础。最后，BioPlex结合其他方法可以用来揭示具有生物学或临床意义的相互作用。例如，与家族性肌萎缩侧索硬化症有关的膜蛋白VAPB的突变扰乱了一个明确的相互作用群体。
Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally-related proteins. Finally, BioPlex, in combination with other approaches can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial Amyotrophic Lateral Sclerosis perturb a defined community of interactors.