Genetic interaction mapping informs integrative structure determination of protein complexes
Category
Published on
Type
journal-article
Author
Hannes Braberg and Ignacia Echeverria and Stefan Bohn and Peter Cimermancic and Anthony Shiver and Richard Alexander and Jiewei Xu and Michael Shales and Raghuvar Dronamraju and Shuangying Jiang and Gajendradhar Dwivedi and Derek Bogdanoff and Kaitlin K. Chaung and Ruth Hüttenhain and Shuyi Wang and David Mavor and Riccardo Pellarin and Dina Schneidman and Joel S. Bader and James S. Fraser and John Morris and James E. Haber and Brian D. Strahl and Carol A. Gross and Junbiao Dai and Jef D. Boeke and Andrej Sali and Nevan J. Krogan
Citation
Braberg, H. et al., 2020. Genetic interaction mapping informs integrative structure determination of protein complexes. Science, 370(6522), p.eaaz4910. Available at: http://dx.doi.org/10.1126/science.aaz4910.
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.