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| | ==Crystal structure of LprG mutant V91W from Mycobacterium tuberculosis== | | ==Crystal structure of LprG mutant V91W from Mycobacterium tuberculosis== |
| - | <StructureSection load='3mh9' size='340' side='right' caption='[[3mh9]], [[Resolution|resolution]] 1.79Å' scene=''> | + | <StructureSection load='3mh9' size='340' side='right'caption='[[3mh9]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mh9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MH9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mh9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MH9 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mh8|3mh8]], [[3mha|3mha]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3mh8|3mh8]], [[3mha|3mha]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpp-27, lprG, MT1455, MTCY21B4.28c, Rv1411c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpp-27, lprG, MT1455, MTCY21B4.28c, Rv1411c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=3mh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mh9 OCA], [http://pdbe.org/3mh9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mh9 RCSB], [http://www.ebi.ac.uk/pdbsum/3mh9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mh9 ProSAT]</span></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=3mh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mh9 OCA], [https://pdbe.org/3mh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mh9 RCSB], [https://www.ebi.ac.uk/pdbsum/3mh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mh9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LPRG_MYCTU LPRG_MYCTU]] TLR2 agonist that can inhibit primary human macrophage MHC-II Ag processing. Required for Rv1410c (P55) activity.<ref>PMID:15294983</ref> <ref>PMID:18156250</ref> | + | [[https://www.uniprot.org/uniprot/LPRG_MYCTU LPRG_MYCTU]] TLR2 agonist that can inhibit primary human macrophage MHC-II Ag processing. Required for Rv1410c (P55) activity.<ref>PMID:15294983</ref> <ref>PMID:18156250</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Myctu]] | | [[Category: Myctu]] |
| | [[Category: Sacchettini, J C]] | | [[Category: Sacchettini, J C]] |
| Structural highlights
Function
[LPRG_MYCTU] TLR2 agonist that can inhibit primary human macrophage MHC-II Ag processing. Required for Rv1410c (P55) activity.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a glycolipid binding function of LprG that enhances recognition of triacylated MTB glycolipids by TLR2 and may affect glycolipid assembly or transport for bacterial cell wall biogenesis.
Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.,Drage MG, Tsai HC, Pecora ND, Cheng TY, Arida AR, Shukla S, Rojas RE, Seshadri C, Moody DB, Boom WH, Sacchettini JC, Harding CV Nat Struct Mol Biol. 2010 Aug 8. PMID:20694006[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gehring AJ, Dobos KM, Belisle JT, Harding CV, Boom WH. Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing. J Immunol. 2004 Aug 15;173(4):2660-8. PMID:15294983
- ↑ Farrow MF, Rubin EJ. Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein. J Bacteriol. 2008 Mar;190(5):1783-91. Epub 2007 Dec 21. PMID:18156250 doi:10.1128/JB.01046-07
- ↑ Drage MG, Tsai HC, Pecora ND, Cheng TY, Arida AR, Shukla S, Rojas RE, Seshadri C, Moody DB, Boom WH, Sacchettini JC, Harding CV. Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2. Nat Struct Mol Biol. 2010 Aug 8. PMID:20694006 doi:10.1038/nsmb.1869
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