2z62

From Proteopedia

(Difference between revisions)

Revision as of 11:24, 7 October 2017

Crystal structure of the TV3 hybrid of human TLR4 and hagfish VLRB.61

Structural highlights

2z62 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2z63, 2z64, 2z65, 2z66
Gene:	TLR4, VLRB.61 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TLR4_HUMAN] Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:611488]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.

Function

[TLR4_HUMAN] Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific.^[1]

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

TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex. We determined the structure of the full-length ectodomain of the mouse TLR4 and MD-2 complex. We also produced a series of hybrids of human TLR4 and hagfish VLR and determined their structures with and without bound MD-2 and Eritoran. TLR4 is an atypical member of the LRR family and is composed of N-terminal, central, and C-terminal domains. The beta sheet of the central domain shows unusually small radii and large twist angles. MD-2 binds to the concave surface of the N-terminal and central domains. The interaction with Eritoran is mediated by a hydrophobic internal pocket in MD-2. Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS.

Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.,Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO Cell. 2007 Sep 7;130(5):906-17. PMID:17803912^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schmidt M, Raghavan B, Muller V, Vogl T, Fejer G, Tchaptchet S, Keck S, Kalis C, Nielsen PJ, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA, Goebeler M. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol. 2010 Sep;11(9):814-9. doi: 10.1038/ni.1919. Epub 2010 Aug 15. PMID:20711192 doi:10.1038/ni.1919
↑ Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 2007 Sep 7;130(5):906-17. PMID:17803912 doi:http://dx.doi.org/10.1016/j.cell.2007.08.002

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2z62"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the TV3 hybrid of human TLR4 and hagfish VLRB.61==
 <StructureSection load='2z62' size='340' side='right' caption='[[2z62]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z63|2z63]], [[2z64|2z64]], [[2z65|2z65]], [[2z66|2z66]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR4, VLRB.61 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2z62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z62 OCA], [http://pdbe.org/2z62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z62 RCSB], [http://www.ebi.ac.uk/pdbsum/2z62 PDBsum]</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=2z62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z62 OCA], [http://pdbe.org/2z62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z62 RCSB], [http://www.ebi.ac.uk/pdbsum/2z62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2z62 ProSAT]</span></td></tr>
 </table>
 == Disease ==

2z62

From Proteopedia

Revision as of 11:24, 7 October 2017

Crystal structure of the TV3 hybrid of human TLR4 and hagfish VLRB.61

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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