Integration host factor bends and bridges DNA in a multiplicity of binding modes with varying specificity

Abstract Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2021-09, Vol.49 (15), p.8684-8698
Main Authors: Yoshua, Samuel B, Watson, George D, Howard, Jamieson A L, Velasco-Berrelleza, Victor, Leake, Mark C, Noy, Agnes
Format: Article
Language:English
Subjects:
Genome Integrity, Repair and
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends in DNA at sequences relevant to several functions including transcription and recombination, and is also responsible for general DNA compaction when bound non-specifically. We show that IHF–DNA structural multimodality is more elaborate than previously thought, and provide insights into how this drives mechanical switching towards strongly bent DNA. Using single-molecule atomic force microscopy and atomic molecular dynamics simulations we find three binding modes in roughly equal proportions: ‘associated’ (73° of DNA bend), ‘half-wrapped’ (107°) and ‘fully-wrapped’ (147°), only the latter occurring with sequence specificity. We show IHF bridges two DNA double helices through non-specific recognition that gives IHF a stoichiometry greater than one and enables DNA mesh assembly. We observe that IHF-DNA structural multiplicity is driven through non-specific electrostatic interactions that we anticipate to be a general NAP feature for physical organization of chromosomes.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkab641