Lymphocyte antigen 96 (original) (raw)

From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens

LY96
Available structuresPDBOrtholog search: PDBe RCSB List of PDB id codes2E56, 2E59, 2Z65, 3FXI, 3ULA, 4G8A
Identifiers
Aliases LY96, ESOP-1, MD-2, MD2, ly-96, lymphocyte antigen 96
External IDs OMIM: 605243; MGI: 1341909; HomoloGene: 9109; GeneCards: LY96; OMA:LY96 - orthologs
Gene location (Human)Chromosome 8 (human)Chr.Chromosome 8 (human)[1]Chromosome 8 (human)Genomic location for LY96Genomic location for LY96Band8q21.11Start73,991,392 bp[1]End74,029,079 bp[1]
Gene location (Mouse)Chromosome 1 (mouse)Chr.Chromosome 1 (mouse)[2]Chromosome 1 (mouse)Genomic location for LY96Genomic location for LY96Band1|1 A3Start16,758,275 bp[2]End16,779,835 bp[2]
RNA expression patternBgeeHuman Mouse (ortholog)Top expressed inmonocyteperiodontal fibergranulocytespleentesticleappendixlymph nodegallbladderdeciduatrabecular boneTop expressed inblastocystgranulocytemorularight kidneyzygoteseminal vesiculaparotid glandepithelium of small intestineproximal tubuleembryoMore reference expression dataBioGPSMore reference expression data
Gene ontologyMolecular function coreceptor activity protein binding lipopolysaccharide immune receptor activity lipopolysaccharide binding Toll-like receptor 4 binding Cellular component intrinsic component of plasma membrane plasma membrane extracellular region lipopolysaccharide receptor complex endosome membrane extracellular space Biological process toll-like receptor 4 signaling pathway immune system process MyD88-dependent toll-like receptor signaling pathway positive regulation of lipopolysaccharide-mediated signaling pathway TRIF-dependent toll-like receptor signaling pathway cellular defense response cell surface receptor signaling pathway response to lipopolysaccharide positive regulation of tumor necrosis factor production inflammatory response cellular response to lipopolysaccharide detection of lipopolysaccharide I-kappaB kinase/NF-kappaB signaling MyD88-independent toll-like receptor signaling pathway lipopolysaccharide-mediated signaling pathway negative regulation of MyD88-independent toll-like receptor signaling pathway innate immune response necroptosis apoptotic signaling pathway toll-like receptor signaling pathway Sources:Amigo / QuickGO
OrthologsSpeciesHuman MouseEntrez2364317087EnsemblENSG00000154589ENSMUSG00000025779UniProtQ9Y6Y9Q9JHF9RefSeq (mRNA)NM_001195797NM_015364NM_001159711NM_016923RefSeq (protein)NP_001182726NP_056179NP_001153183NP_058619Location (UCSC)Chr 8: 73.99 – 74.03 MbChr 1: 16.76 – 16.78 MbPubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Lymphocyte antigen 96, also known as "Myeloid Differentiation factor 2 (MD-2)," is a protein that in humans is encoded by the LY96 gene.[5][6][7][8]

The protein encoded by this gene is involved in binding lipopolysaccharide with Toll-Like Receptor (TLR4).

The MD-2 protein appears to associate with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccharide (LPS), thus providing a link between the receptor and LPS signaling.[7] That is, the primary interface between TLR4 and MD-2 is formed before binding LPS and the dimerization interface is induced by binding LPS.[8]

MD-2 has a β-cup fold structure composed of two anti-parallel β sheets forming a large hydrophobic pocket for ligand binding.[9][10]

Lymphocyte antigen 96 has been shown to interact with TLR 4.[5][11]

When LPS binds to a hydrophobic pocket in MD-2, it directly mediates dimerization of the two TLR4-MD-2 complexes. Thus, TLR4 and MD-2 form a heterodimer that recognizes a common pattern in structurally diverse LPS molecules. These interactions allow TLR4 to recognize LPS.[8] Macrophages in MD-2 knockout mice are unresponsive to LPS.[12]

LPS is extracted from the bacterial membrane and transferred to TLR4-MD-2 by two accessory proteins, LPS-binding protein and CD14, to induce innate immune response.[8]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000154589 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025779 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, et al. (June 1999). "MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4". The Journal of Experimental Medicine. 189 (11): 1777–82. doi:10.1084/jem.189.11.1777. PMC 2193086. PMID 10359581.
  6. ^ Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M (August 2001). "Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide". Journal of Immunology. 167 (3): 1609–16. doi:10.4049/jimmunol.167.3.1609. PMID 11466383.
  7. ^ a b "Entrez Gene: LY96 lymphocyte antigen 96".
  8. ^ a b c d Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (April 2009). "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex". Nature. 458 (7242): 1191–5. Bibcode:2009Natur.458.1191P. doi:10.1038/nature07830. PMID 19252480. S2CID 4396446.
  9. ^ Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, et al. (September 2007). "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran". Cell. 130 (5): 906–17. doi:10.1016/j.cell.2007.08.002. PMID 17803912. S2CID 18948568.
  10. ^ Ohto U, Fukase K, Miyake K, Satow Y (June 2007). "Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa". Science. 316 (5831): 1632–4. Bibcode:2007Sci...316.1632O. doi:10.1126/science.1139111. PMID 17569869. S2CID 37539892.
  11. ^ Re F, Strominger JL (June 2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". The Journal of Biological Chemistry. 277 (26): 23427–32. doi:10.1074/jbc.M202554200. PMID 11976338.
  12. ^ Ciesielska A, Matyjek M, Kwiatkowska K (2021). "TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling". Cellular and Molecular Life Sciences. 78 (4): 1233–1261. doi:10.1007/s00018-020-03656-y. PMC 7904555. PMID 33057840.

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations