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| ==Crystal structure of the dimerization domain of Lsr2 from Mycobacterium tuberculosis in the P 1 21 1 space group== | | ==Crystal structure of the dimerization domain of Lsr2 from Mycobacterium tuberculosis in the P 1 21 1 space group== |
| <StructureSection load='4e1p' size='340' side='right' caption='[[4e1p]], [[Resolution|resolution]] 1.73Å' scene=''> | | <StructureSection load='4e1p' size='340' side='right'caption='[[4e1p]], [[Resolution|resolution]] 1.73Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4e1p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E1P FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4e1p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E1P FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e1r|4e1r]]</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.728Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lsr2, MT3704, MTCY07H7B.25, Rv3597c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1p OCA], [https://pdbe.org/4e1p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e1p RCSB], [https://www.ebi.ac.uk/pdbsum/4e1p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1p ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1p OCA], [http://pdbe.org/4e1p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e1p RCSB], [http://www.ebi.ac.uk/pdbsum/4e1p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1p ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/LSR2_MYCTU LSR2_MYCTU]] DNA-bridging protein that has both architectural and regulatory roles. Influences the organization of chromatin and gene expression by binding non-specifically to DNA, with a preference for AT-rich sequences, and bridging distant DNA segments. Represses expression of multiple genes involved in a broad range of cellular processes, including major virulence factors or antibiotic-induced genes, such as iniBAC or efpA. May coordinate global gene regulation and virulence. Also protects mycobacteria against reactive oxygen intermediates during macrophage infection by acting as a physical barrier to DNA degradation.<ref>PMID:17590082</ref> <ref>PMID:18187505</ref> <ref>PMID:19237572</ref> <ref>PMID:20133735</ref> | | [https://www.uniprot.org/uniprot/LSR2_MYCTU LSR2_MYCTU] DNA-bridging protein that has both architectural and regulatory roles. Influences the organization of chromatin and gene expression by binding non-specifically to DNA, with a preference for AT-rich sequences, and bridging distant DNA segments. Represses expression of multiple genes involved in a broad range of cellular processes, including major virulence factors or antibiotic-induced genes, such as iniBAC or efpA. May coordinate global gene regulation and virulence. Also protects mycobacteria against reactive oxygen intermediates during macrophage infection by acting as a physical barrier to DNA degradation.<ref>PMID:17590082</ref> <ref>PMID:18187505</ref> <ref>PMID:19237572</ref> <ref>PMID:20133735</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Lsr2 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 A 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 beta-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.
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| The structure of the oligomerization domain of Lsr2 from Mycobacterium tuberculosis reveals a mechanism for chromosome organization and protection.,Summers EL, Meindl K, Uson I, Mitra AK, Radjainia M, Colangeli R, Alland D, Arcus VL PLoS One. 2012;7(6):e38542. doi: 10.1371/journal.pone.0038542. Epub 2012 Jun 13. PMID:22719899<ref>PMID:22719899</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4e1p" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Arcus, V L]] | | [[Category: Large Structures]] |
| [[Category: Meindl, K]] | | [[Category: Mycobacterium tuberculosis]] |
| [[Category: Summers, E L]] | | [[Category: Arcus VL]] |
| [[Category: Uson, I]] | | [[Category: Meindl K]] |
| [[Category: Anti-parallel beta sheet]] | | [[Category: Summers EL]] |
| [[Category: Dimer]] | | [[Category: Uson I]] |
| [[Category: Dna binding protein]]
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