학술논문
Integrative structure determination of histones H3 and H4 using genetic interactions.
Document Type
Academic Journal
Author
Echeverria I; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.; Quantitative Biosciences Institute, University of California, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.; Braberg H; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.; Quantitative Biosciences Institute, University of California, San Francisco, CA, USA.; Krogan NJ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.; Quantitative Biosciences Institute, University of California, San Francisco, CA, USA.; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.; Sali A; Quantitative Biosciences Institute, University of California, San Francisco, CA, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
Source
Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-4658 (Electronic) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE
Subject
Language
English
Abstract
Integrative structure modeling is increasingly used for determining the architectures of biological assemblies, especially those that are structurally heterogeneous. Recently, we reported on how to convert in vivo genetic interaction measurements into spatial restraints for structural modeling: first, phenotypic profiles are generated for each point mutation and thousands of gene deletions or environmental perturbations. Following, the phenotypic profile similarities are converted into distance restraints on the pairs of mutated residues. We illustrate the approach by determining the structure of the histone H3-H4 complex. The method is implemented in our open-source IMP program, expanding the structural biology toolbox by allowing structural characterization based on in vivo data without the need to purify the target system. We compare genetic interaction measurements to other sources of structural information, such as residue coevolution and deep-learning structure prediction of complex subunits. We also suggest that determining genetic interactions could benefit from new technologies, such as CRISPR-Cas9 approaches to gene editing, especially for mammalian cells. Finally, we highlight the opportunity for using genetic interactions to determine recalcitrant biomolecular structures, such as those of disordered proteins, transient protein assemblies, and host-pathogen protein complexes.
(© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
(© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)