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Genetic interaction mapping informs integrative structure determination of protein complexes.
Braberg, Hannes; Echeverria, Ignacia; Bohn, Stefan; Cimermancic, Peter; Shiver, Anthony; Alexander, Richard; Xu, Jiewei; Shales, Michael; Dronamraju, Raghuvar; Jiang, Shuangying; Dwivedi, Gajendradhar; Bogdanoff, Derek; Chaung, Kaitlin K; Hüttenhain, Ruth; Wang, Shuyi; Mavor, David; Pellarin, Riccardo; Schneidman, Dina; Bader, Joel S; Fraser, James S; Morris, John; Haber, James E; Strahl, Brian D; Gross, Carol A; Dai, Junbiao; Boeke, Jef D; Sali, Andrej; Krogan, Nevan J.
Affiliation
  • Braberg H; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Echeverria I; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Bohn S; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Cimermancic P; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Shiver A; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Alexander R; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Xu J; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Shales M; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Dronamraju R; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Jiang S; Graduate Group in Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
  • Dwivedi G; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Bogdanoff D; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Chaung KK; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Hüttenhain R; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Wang S; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Mavor D; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Pellarin R; Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Schneidman D; CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Chin
  • Bader JS; Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454, USA.
  • Fraser JS; Center for Advanced Technology, Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Morris J; Center for Advanced Technology, Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Haber JE; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Strahl BD; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gross CA; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Dai J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Boeke JD; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Sali A; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Krogan NJ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Science ; 370(6522)2020 12 11.
Article in En | MEDLINE | ID: mdl-33303586
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Saccharomyces cerevisiae / Saccharomyces cerevisiae Proteins / Multiprotein Complexes / Protein Interaction Maps Language: En Journal: Science Year: 2020 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Saccharomyces cerevisiae / Saccharomyces cerevisiae Proteins / Multiprotein Complexes / Protein Interaction Maps Language: En Journal: Science Year: 2020 Document type: Article Affiliation country: