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Lymphocyte antigen 96

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LY96
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLY96, ESOP-1, MD-2, MD2, ly-96, lymphocyte antigen 96
External IDsOMIM: 605243; MGI: 1341909; HomoloGene: 9109; GeneCards: LY96; OMA:LY96 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001195797
NM_015364

NM_001159711
NM_016923

RefSeq (protein)

NP_001182726
NP_056179

NP_001153183
NP_058619

Location (UCSC)Chr 8: 73.99 – 74.03 MbChr 1: 16.76 – 16.78 Mb
PubMed 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).

Function

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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]

Structure

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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]

Interactions

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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, 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]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000154589Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025779Ensembl, 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.

Further reading

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