1yxk

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Crystal structure of human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) disulfide-linked dimer

Structural highlights

1yxk is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OLR1_HUMAN Note=Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility.[1] [2] [3] [4] [5] 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.[6] [7] [8] [9] [10]

Function

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.[11] [12] [13]

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

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[14]

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

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See Also

References

  1. ↑ Luedecking-Zimmer E, DeKosky ST, Chen Q, Barmada MM, Kamboh MI. Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Hum Genet. 2002 Oct;111(4-5):443-51. Epub 2002 Aug 16. PMID:12384789 doi:10.1007/s00439-002-0802-7
  2. ↑ Lambert JC, Luedecking-Zimmer E, Merrot S, Hayes A, Thaker U, Desai P, Houzet A, Hermant X, Cottel D, Pritchard A, Iwatsubo T, Pasquier F, Frigard B, Conneally PM, Chartier-Harlin MC, DeKosky ST, Lendon C, Mann D, Kamboh MI, Amouyel P. Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease. J Med Genet. 2003 Jun;40(6):424-30. PMID:12807963
  3. ↑ Bertram L, Parkinson M, Mullin K, Menon R, Blacker D, Tanzi RE. No association between a previously reported OLR1 3' UTR polymorphism and Alzheimer's disease in a large family sample. J Med Genet. 2004 Apr;41(4):286-8. PMID:15060104
  4. ↑ Pritchard A, St Clair D, Lemmon H, Mann DM, Lendon C. No association between polymorphisms in the lectin-like oxidised low density lipoprotein receptor (ORL1) gene on chromosome 12 and Alzheimer's disease in a UK cohort. Neurosci Lett. 2004 Aug 12;366(2):126-9. PMID:15276231 doi:10.1016/j.neulet.2004.05.023
  5. ↑ D'Introno A, Solfrizzi V, Colacicco AM, Capurso C, Torres F, Capurso SA, Capurso A, Panza F. Polymorphisms in the oxidized low-density lipoprotein receptor-1 gene and risk of Alzheimer's disease. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):280-4. PMID:15860461
  6. ↑ Luedecking-Zimmer E, DeKosky ST, Chen Q, Barmada MM, Kamboh MI. Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Hum Genet. 2002 Oct;111(4-5):443-51. Epub 2002 Aug 16. PMID:12384789 doi:10.1007/s00439-002-0802-7
  7. ↑ Lambert JC, Luedecking-Zimmer E, Merrot S, Hayes A, Thaker U, Desai P, Houzet A, Hermant X, Cottel D, Pritchard A, Iwatsubo T, Pasquier F, Frigard B, Conneally PM, Chartier-Harlin MC, DeKosky ST, Lendon C, Mann D, Kamboh MI, Amouyel P. Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease. J Med Genet. 2003 Jun;40(6):424-30. PMID:12807963
  8. ↑ Bertram L, Parkinson M, Mullin K, Menon R, Blacker D, Tanzi RE. No association between a previously reported OLR1 3' UTR polymorphism and Alzheimer's disease in a large family sample. J Med Genet. 2004 Apr;41(4):286-8. PMID:15060104
  9. ↑ Pritchard A, St Clair D, Lemmon H, Mann DM, Lendon C. No association between polymorphisms in the lectin-like oxidised low density lipoprotein receptor (ORL1) gene on chromosome 12 and Alzheimer's disease in a UK cohort. Neurosci Lett. 2004 Aug 12;366(2):126-9. PMID:15276231 doi:10.1016/j.neulet.2004.05.023
  10. ↑ D'Introno A, Solfrizzi V, Colacicco AM, Capurso C, Torres F, Capurso SA, Capurso A, Panza F. Polymorphisms in the oxidized low-density lipoprotein receptor-1 gene and risk of Alzheimer's disease. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):280-4. PMID:15860461
  11. ↑ Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997 Mar 6;386(6620):73-7. PMID:9052782 doi:10.1038/386073a0
  12. ↑ Hayashida K, Kume N, Minami M, Kita T. Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions. FEBS Lett. 2002 Jan 30;511(1-3):133-8. PMID:11821063
  13. ↑ Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P. Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 2002 Sep;17(3):353-62. PMID:12354387
  14. ↑ Ohki I, Ishigaki T, Oyama T, Matsunaga S, Xie Q, Ohnishi-Kameyama M, Murata T, Tsuchiya D, Machida S, Morikawa K, Tate S. Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure. 2005 Jun;13(6):905-17. PMID:15939022 doi:10.1016/j.str.2005.03.016

Contents


PDB ID 1yxk

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