Lymphocyte antigen 96

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. That is, the primary interface between TLR4 and MD-2 is formed before binding LPS and the dimerization interface is induced by binding LPS.

MD-2 has a β-cup fold structure composed of two anti-parallel β sheets forming a large hydrophobic pocket for ligand binding.{{cite journal | vauthors = Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO | title = Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran | journal = Cell | volume = 130 | issue = 5 | pages = 906–17 | date = September 2007 | pmid = 17803912 | doi = 10.1016/j.cell.2007.08.002 | s2cid = 18948568 | doi-access = free }}{{cite journal | vauthors = Ohto U, Fukase K, Miyake K, Satow Y | title = Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa | journal = Science | volume = 316 | issue = 5831 | pages = 1632–4 | date = June 2007 | pmid = 17569869 | doi = 10.1126/science.1139111 | bibcode = 2007Sci...316.1632O | s2cid = 37539892 }}

Lymphocyte antigen 96 has been shown to interact with TLR 4.{{cite journal | vauthors = Re F, Strominger JL | title = Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness | journal = The Journal of Biological Chemistry | volume = 277 | issue = 26 | pages = 23427–32 | date = June 2002 | pmid = 11976338 | doi = 10.1074/jbc.M202554200 | doi-access = free }}

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. Macrophages in MD-2 knockout mice are unresponsive to LPS.{{cite journal | vauthors = Ciesielska A, Matyjek M, Kwiatkowska K | title = TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling | journal = Cellular and Molecular Life Sciences | volume = 78 | issue=4 | pages = 1233–1261 | date=2021 | doi = 10.1007/s00018-020-03656-y | pmc=7904555 | pmid = 33057840}}

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.

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Image:Toll-like receptor pathways revised.jpg

• {{MeshName|lymphocyte+antigen+96,+human}}

{{TLR signaling pathway}}