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3ula

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Revision as of 06:30, 5 August 2016

Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex

Structural highlights

3ula is a 4 chain structure with sequence from Bdellostoma burgeri and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3ul7, 3ul8, 3ul9
Gene:	TLR4, VLRB (Bdellostoma burgeri), LY96, ESOP1, MD2 (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] [LY96_HUMAN] Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both MD2 and TLR4, but not TLR4 alone, respond to LPS.

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ula"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex==
 <StructureSection load='3ula' size='340' side='right' caption='[[3ula]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ula]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eptatretus_burgeri Eptatretus burgeri] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ULA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ULA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ula]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bdellostoma_burgeri Bdellostoma burgeri] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ULA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ULA 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=E55:3-O-DECYL-2-DEOXY-6-O-{2-DEOXY-3-O-[(3R)-3-METHOXYDECYL]-6-O-METHYL-2-[(11Z)-OCTADEC-11-ENOYLAMINO]-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSYL}-2-[(3-OXOTETRADECANOYL)AMINO]-1-O-PHOSPHONO-ALPHA-D-GLUCOPYRANOSE'>E55</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ul7|3ul7]], [[3ul8|3ul8]], [[3ul9|3ul9]]</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 Eptatretus burgeri]), LY96, ESOP1, MD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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]), LY96, ESOP1, MD2 ([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=3ula FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ula OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ula RCSB], [http://www.ebi.ac.uk/pdbsum/3ula 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=3ula FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ula OCA], [http://pdbe.org/3ula PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ula RCSB], [http://www.ebi.ac.uk/pdbsum/3ula PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ula ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ula" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 30: @@
 __TOC__
 </StructureSection>
-[[Category: Eptatretus burgeri]]
+[[Category: Bdellostoma burgeri]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Cheong, H K]]
 [[Category: Jeon, Y H]]

3ula

From Proteopedia

Revision as of 06:30, 5 August 2016

Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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