View source for 1yxk


==Crystal structure of human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) disulfide-linked dimer==
<StructureSection load='1yxk' size='340' side='right'caption='[[1yxk]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1yxk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YXK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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=1yxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxk OCA], [https://pdbe.org/1yxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yxk RCSB], [https://www.ebi.ac.uk/pdbsum/1yxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/OLR1_HUMAN OLR1_HUMAN] Note=Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility.<ref>PMID:12384789</ref> <ref>PMID:12807963</ref> <ref>PMID:15060104</ref> <ref>PMID:15276231</ref> <ref>PMID:15860461</ref>   Note=OLR1 may be involved in Alzheimer disease (AD). Involvement in AD is however unclear: according to some authors (PubMed:12354387, PubMed:12810610 and PubMed:15976314), variations in OLR1 modify the risk of AD, while according to other (PubMed:15000751 and PubMed:15060104) they do not.<ref>PMID:12384789</ref> <ref>PMID:12807963</ref> <ref>PMID:15060104</ref> <ref>PMID:15276231</ref> <ref>PMID:15860461</ref> 
== Function ==
[https://www.uniprot.org/uniprot/OLR1_HUMAN OLR1_HUMAN] Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria.<ref>PMID:9052782</ref> <ref>PMID:11821063</ref> <ref>PMID:12354387</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yx/1yxk_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yxk ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lectin-like, oxidized low-density lipoprotein (LDL) receptor 1, LOX-1, is the major receptor for oxidized LDL (OxLDL) in endothelial cells. We have determined the crystal structure of the ligand binding domain of LOX-1, with a short stalk region connecting the domain to the membrane-spanning region, as a homodimer linked by an interchain disulfide bond. In vivo assays with LOX-1 mutants revealed that the "basic spine," consisting of linearly aligned arginine residues spanning over the dimer surface, is responsible for ligand binding. Single amino acid substitution in the dimer interface caused a severe reduction in LOX-1 binding activity, suggesting that the correct dimer arrangement is crucial for binding to OxLDL. Based on the LDL model structure, possible binding modes of LOX-1 to OxLDL are proposed.

Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL.,Ohki I, Ishigaki T, Oyama T, Matsunaga S, Xie Q, Ohnishi-Kameyama M, Murata T, Tsuchiya D, Machida S, Morikawa K, Tate S Structure. 2005 Jun;13(6):905-17. PMID:15939022<ref>PMID:15939022</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1yxk" style="background-color:#fffaf0;"></div>

==See Also==
*[[LDL receptor|LDL receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ishigaki T]]
[[Category: Machida S]]
[[Category: Matsunaga S]]
[[Category: Morikawa K]]
[[Category: Murata T]]
[[Category: Ohki I]]
[[Category: Ohnishi-Kameyama M]]
[[Category: Oyama T]]
[[Category: Tate S]]
[[Category: Tsuchiya D]]
[[Category: Xie Q]]