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Cell Syst DOI:10.1016/j.cels.2018.04.011

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

Publication TypeJournal Article
Year of Publication2018
AuthorsPan, 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
JournalCell Syst
Volume6
Issue5
Pages555-568.e7
Date Published2018 May 23
ISSN2405-4712
Abstract

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 that 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.

DOI10.1016/j.cels.2018.04.011
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29778836?dopt=Abstract

Alternate JournalCell Syst
PubMed ID29778836