Genetic interaction mapping informs integrative structure determination of protein complexes.

摘要: 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 genetic interactions. We construct phenotypic profiles point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two into upper bound the distance mutated residues. determine yeast histone H3-H4 complex based ~500,000 interactions 350 mutants. then apply method subunits Rpb1-Rpb2 RNA polymerase II and RpoB-RpoC bacterial polymerase. The accuracy comparable chemical cross-links; using restraints from both cross-links further improves model precision. provides efficient means augment with observations.