Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.
Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.
复制标题
DOI：
10.1016/j.cels.2018.04.011
复制
发表时间：
2018-05-23
期刊：
影响因子：
9.3
通讯作者：
Kadoch C
中科院分区：
文献类型：
--
作者：
Pan J;Meyers RM;Michel BC;Mashtalir N;Sizemore AE;Wells JN;Cassel SH;Vazquez F;Weir BA;Hahn WC;Marsh JA;Tsherniak A;Kadoch C
蛋白质复合物是在细胞环境中共同进化以执行一个或多个协调功能的亚基的组装体。哺乳动物蛋白质复合物的功能注释对于理解生物过程以及疾病机制至关重要。在这里，我们使用了来自基因组规模的RNAi和CRISPR-Cas9的健身屏幕在数百个人类癌细胞系进行分配功能相似性的措施。从这些措施中，我们系统地建立和功能相似性网络的特点概括了已知的结构和功能的特点，充分研究的蛋白质复合物和解决新的功能模块内缺乏结构分辨率的复合物，如哺乳动物SWI/SNF复合物。最后，通过将功能网络与大的蛋白质-蛋白质相互作用网络相结合，我们发现了新的蛋白质复合物，涉及最近进化的未知功能的基因。两者合计，这些发现表明遗传扰动屏幕单独和结合大规模的生物物理数据，以提高我们的理解哺乳动物蛋白质复合物在正常和疾病状态的效用。
Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9- based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks which recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently-evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone and in combination with large-scale biophysical data to enhance our understanding of mammalian protein complexes in normal and disease states.
登录
查看更多内容
哺乳动物SWI/SNF复合物的蛋白质组学和生物信息学分析确定了在人类恶性肿瘤中的广泛作用。
影响因子：
30.8
作者：
Kadoch, Cigall;Hargreaves, Diana C.;Hodges, Courtney;Elias, Laura;Ho, Lena;Ranish, Jeff;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
影响因子：
16
作者：
Jeronimo C;Langelier MF;Bataille AR;Pascal JM;Pugh BF;Robert F
通讯作者：
Robert F
影响因子：
9.9
作者：
Drew K;Lee C;Huizar RL;Tu F;Borgeson B;McWhite CD;Ma Y;Wallingford JB;Marcotte EM
通讯作者：
Marcotte EM
影响因子：
56.9
作者：
Blomen, Vincent A.;Majek, Peter;Brummelkamp, Thijn R.
通讯作者：
Brummelkamp, Thijn R.
影响因子：
64.5
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
通讯作者：
Gygi SP