| Literature DB >> 33303586 |
Hannes Braberg1,2, Ignacia Echeverria1,2,3, Stefan Bohn1,2,4, Peter Cimermancic3, Anthony Shiver5, Richard Alexander1, Jiewei Xu1,2,4, Michael Shales1,2, Raghuvar Dronamraju6, Shuangying Jiang7, Gajendradhar Dwivedi8, Derek Bogdanoff9, Kaitlin K Chaung9, Ruth Hüttenhain1,2,4, Shuyi Wang1, David Mavor2,3, Riccardo Pellarin3, Dina Schneidman3, Joel S Bader10, James S Fraser2,3, John Morris11, James E Haber8, Brian D Strahl6, Carol A Gross12, Junbiao Dai7, Jef D Boeke13,14,15,16, Andrej Sali17,3,11, Nevan J Krogan18,2,4,19.
Abstract
Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations.Entities:
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Year: 2020 PMID： 33303586 PMCID： PMC7946025 DOI： 10.1126/science.aaz4910
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728