Cooperative DNA binding by proteins through DNA shape complementarity

Journal Article · Thu Jul 25 00:00:00 EDT 2019 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkz642· OSTI ID:1638899

Hancock, Stephen P. ^[1]; Cascio, Duilio ^[2]; Johnson, Reid C. ^[3]

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1. Department of Biological Chemistry, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1737, USA, Department of Chemistry, Towson University, 8000 York Rd., Towson, MD 21252, USA
2. University of California at Los Angeles-Department of Energy Institute of Genomics and Proteomics, University of California at Los Angeles, Los Angeles, CA 90095-1570, USA
3. Department of Biological Chemistry, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1737, USA, Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA

Abstract

Localized arrays of proteins cooperatively assemble onto chromosomes to control DNA activity in many contexts. Binding cooperativity is often mediated by specific protein–protein interactions, but cooperativity through DNA structure is becoming increasingly recognized as an additional mechanism. During the site-specific DNA recombination reaction that excises phage λ from the chromosome, the bacterial DNA architectural protein Fis recruits multiple λ-encoded Xis proteins to the attR recombination site. Here, we report X-ray crystal structures of DNA complexes containing Fis + Xis, which show little, if any, contacts between the two proteins. Comparisons with structures of DNA complexes containing only Fis or Xis, together with mutant protein and DNA binding studies, support a mechanism for cooperative protein binding solely by DNA allostery. Fis binding both molds the minor groove to potentiate insertion of the Xis β-hairpin wing motif and bends the DNA to facilitate Xis-DNA contacts within the major groove. The Fis-structured minor groove shape that is optimized for Xis binding requires a precisely positioned pyrimidine-purine base-pair step, whose location has been shown to modulate minor groove widths in Fis-bound complexes to different DNA targets.

• Sponsoring Organization: USDOE
• Grant/Contract Number: FC02-02ER63421; AC02-06CH11357
• OSTI ID: 1638899
• Alternate ID(s): OSTI ID: 1562718
• Journal Information: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 16 Vol. 47; ISSN 0305-1048
• Publisher: Oxford University Press
• Country of Publication: United Kingdom
• Language: English