The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection

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dc.contributor.authorSummers, Emma Louise
dc.contributor.authorMeindl, Kathrin
dc.contributor.authorUsón, Isabel
dc.contributor.authorMitra, Alok K.
dc.contributor.authorRadjainia, Mazdak
dc.contributor.authorColangeli, Roberto
dc.contributor.authorAlland, David
dc.contributor.authorArcus, Vickery L.
dc.date.accessioned2012-06-28T04:32:42Z
dc.date.available2012-06-28T04:32:42Z
dc.date.copyright2012-06-13
dc.date.issued2012
dc.description.abstractLsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNA-binding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal cross-linking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 Å resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß-ß-a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel β-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated.en_NZ
dc.format.mimetypeapplication/pdf
dc.identifier.citationSummers, E.L., Meindl, K., Usón, I., Mitra, A.K., Radjainia, M., …, Arcus, V.L. (2012). The structure of the oligomerization domain of Lsr2 from Mycobacterium tuberculosis reveals a mechanism for chromosome organization and protection. PLoS One, 7(6), e38542.en_NZ
dc.identifier.doi10.1371/journal.pone.0038542.t002en_NZ
dc.identifier.urihttps://hdl.handle.net/10289/6431
dc.language.isoen
dc.publisherPublic Library of Scienceen_NZ
dc.relation.isPartOfPlos oneen_NZ
dc.relation.ispartofPLoS ONE
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0038542en_NZ
dc.rightsThis article has been published in the journal: PLoS One. © 2012 Summers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_NZ
dc.subjectbiologyen_NZ
dc.titleThe Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protectionen_NZ
dc.typeJournal Articleen_NZ
pubs.begin-page1en_NZ
pubs.elements-id37678
pubs.end-page12en_NZ
pubs.issue6en_NZ
pubs.volume7en_NZ
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