Genetic interaction mapping informs integrative structure determination of protein complexes

• DOI: 10.1126/science.aaz4910
• Publication Date: 2020-12-10T20:16:10Z
• Authors: Hannes Braberg; Ignacia Echeverria; Stefan Bohn; Peter Cimermancic; Anthony Shiver; Richard Alexander; Jiewei Xu; Michael Shales; Raghuvar Dronamraju; Shuangying Jiang; Gajendradhar Dwivedi; Derek Bogdanoff; Kaitlin K. Chaung; Ruth Hüttenhain; Shuyi Wang; David Mavor; Riccardo Pellarin; Dina Schneidman; Joel S. Bader; James S. Fraser; John Morris; James E. Haber; Brian D. Strahl; Carol A. Gross; Junbiao Dai; Jef D. Boeke; Andrej Sali; Nevan J. Krogan
• Keywords: 570; MESH: Mutation; Saccharomyces cerevisiae Proteins; General Science & Technology; Protein Conformation; 1.1 Normal biological development and functioning; Bioinformatics and Computational Biology; Bioengineering; Saccharomyces cerevisiae; Histones; MESH: Protein Conformation; MESH: Saccharomyces cerevisiae Proteins; Protein Interaction Mapping; Genetics; 2.1 Biological and endogenous factors; Protein Interaction Maps; MESH: Protein Interaction Maps; MESH: Histones; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]; MESH: Protein Interaction Mapping; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology; Biological Sciences; MESH: Multiprotein Complexes; 540; MESH: Saccharomyces cerevisiae; [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics; Multiprotein Complexes; Mutation; Biochemistry and Cell Biology; Generic health relevance

From phenotype to structure

Much insight has come from structures of macromolecular complexes determined by methods such as crystallography or cryo–electron microscopy. However, looking at transient complexes remains challenging, as does determining structures in the context of the cellular environment. Braberg et al. used an integrative approach in which they mapped the phenotypic profiles of a comprehensive set of mutants in a protein complex in the context of gene deletions or environmental perturbations (see the Perspective by Wang). By associating the similarity between phenotypic profiles with the distance between residues, they determined structures for the yeast histone H3-H4 complex, subunits Rpb1-Rpb2 of yeast RNA polymerase II, and subunits RpoB-RpoC of bacterial RNA polymerase. Comparison with known structures shows that the accuracy is comparable to structures determined based on chemical cross-links.

Science , this issue p. eaaz4910 ; see also p. 1269