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| | ==structure of the TV3 mutant M41E== | | ==structure of the TV3 mutant M41E== |
| - | <StructureSection load='3ul9' size='340' side='right' caption='[[3ul9]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='3ul9' size='340' side='right'caption='[[3ul9]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ul9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bdellostoma_burgeri Bdellostoma burgeri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UL9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ul9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bdellostoma_burgeri Bdellostoma burgeri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UL9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3UL9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr> |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ul7|3ul7]], [[3ul8|3ul8]], [[3ula|3ula]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ul7|3ul7]], [[3ul8|3ul8]], [[3ula|3ula]]</td></tr> |
| | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR4, VLRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7764 Bdellostoma burgeri])</td></tr> | | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR4, VLRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7764 Bdellostoma burgeri])</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=3ul9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ul9 OCA], [http://pdbe.org/3ul9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ul9 RCSB], [http://www.ebi.ac.uk/pdbsum/3ul9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ul9 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3ul9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ul9 OCA], [http://pdbe.org/3ul9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ul9 RCSB], [http://www.ebi.ac.uk/pdbsum/3ul9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ul9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3ul9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3ul9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] |
| | + | *[[Variable lymphocyte receptor 3D structures|Variable lymphocyte receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bdellostoma burgeri]] | | [[Category: Bdellostoma burgeri]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Cheong, H K]] | | [[Category: Cheong, H K]] |
| | [[Category: Jeon, Y H]] | | [[Category: Jeon, Y H]] |
| Structural highlights
3ul9 is a 1 chain structure with sequence from Bdellostoma burgeri. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 3ul7, 3ul8, 3ula |
| Gene: | TLR4, VLRB (Bdellostoma burgeri) |
| 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]
Publication Abstract from PubMed
Repeat proteins are increasingly attracting much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural features. Nonetheless, engineering interaction interface and understanding molecular basis for affinity maturation of repeat proteins still remain a challenge. Here, we present a structure-based rational design of a repeat protein with high binding affinity for a target protein. As a model repeat protein, a Toll-like receptor4 (TLR4) decoy receptor composed of leucine-rich repeat (LRR) modules was used, and its interaction interface was rationally engineered to increase the binding affinity for myeloid differentiation protein 2 (MD2). Based on the complex crystal structure of the decoy receptor with MD2, we first designed single amino acid substitutions in the decoy receptor, and obtained three variants showing a binding affinity (K(D)) one-order of magnitude higher than the wild-type decoy receptor. The interacting modes and contributions of individual residues were elucidated by analyzing the crystal structures of the single variants. To further increase the binding affinity, single positive mutations were combined, and two double mutants were shown to have about 3000- and 565-fold higher binding affinities than the wild-type decoy receptor. Molecular dynamics simulations and energetic analysis indicate that an additive effect by two mutations occurring at nearby modules was the major contributor to the remarkable increase in the binding affinities.
Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy receptor with high binding affinity for a target protein.,Han J, Kim HJ, Lee SC, Hong S, Park K, Jeon YH, Kim D, Cheong HK, Kim HS PLoS One. 2012;7(2):e30929. Epub 2012 Feb 17. PMID:22363519[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Han J, Kim HJ, Lee SC, Hong S, Park K, Jeon YH, Kim D, Cheong HK, Kim HS. Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy receptor with high binding affinity for a target protein. PLoS One. 2012;7(2):e30929. Epub 2012 Feb 17. PMID:22363519 doi:10.1371/journal.pone.0030929
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