2z66
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2z66 |SIZE=350|CAPTION= <scene name='initialview01'>2z66</scene>, resolution 1.90Å | |PDB= 2z66 |SIZE=350|CAPTION= <scene name='initialview01'>2z66</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= VLRB.61, TLR4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Eptatretus burgeri, Homo sapiens]) | |GENE= VLRB.61, TLR4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Eptatretus burgeri, Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2z62|2Z62]], [[2z63|2Z63]], [[2z64|2Z64]], [[2z65|2Z65]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z66 OCA], [http://www.ebi.ac.uk/pdbsum/2z66 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2z66 RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603030 603030]], Endotoxin hyporesponsiveness OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603030 603030]], Longevity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603030 603030]], Macular degeneration, age-related, 10 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603030 603030]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 28: | Line 28: | ||
[[Category: Lee, J O.]] | [[Category: Lee, J O.]] | ||
[[Category: Park, B S.]] | [[Category: Park, B S.]] | ||
| - | [[Category: SO4]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
[[Category: immune response]] | [[Category: immune response]] | ||
| Line 43: | Line 42: | ||
[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:18:56 2008'' |
Revision as of 02:18, 31 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | VLRB.61, TLR4 (Eptatretus burgeri, Homo sapiens) | ||||||
| Related: | 2Z62, 2Z63, 2Z64, 2Z65
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the VT3 hybrid of human TLR4 and hagfish VLRB.61
Overview
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.
About this Structure
2Z66 is a Single protein structure of sequence from Eptatretus burgeri, homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 05:18:56 2008
