Lymphocyte antigen 96

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]

LY96
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E56, 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) Chr. Chromosome 8 (human)[1] Band 8q21.11 Start 73,991,392 bp[1] End 74,029,079 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 A3 Start 16,758,275 bp[2] End 16,779,835 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte periodontal fiber granulocyte spleen testicle appendix lymph node gallbladder decidua trabecular bone Top expressed in blastocyst granulocyte morula right kidney zygote seminal vesicula parotid gland epithelium of small intestine proximal tubule embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular 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
Orthologs Species Human Mouse Entrez 23643 17087 Ensembl ENSG00000154589 ENSMUSG00000025779 UniProt Q9Y6Y9 Q9JHF9 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 Mb Chr 1: 16.76 – 16.78 Mb PubMed search [3] [4]
Wikidata
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The protein encoded by this gene is involved in binding lipopolysaccharide with Toll-Like Receptor (TLR4).

Function

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

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

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]