Lymphocyte antigen 96 (MD-2) (MD-2)

Lymphocyte antigen 96 (MD-2) is a secreted glycoprotein that non-covalently associates with the extracellular domain of Toll-like receptor 4 (TLR4) (UniProt Q9Y6Y9). It is essential for the recognition of lipopolysaccharide (LPS) from Gram-negative bacteria, as TLR4 alone cannot bind LPS (PubMed: 10359807). MD-2 contains a large hydrophobic pocket that directly accommodates the lipid A portion of LPS, which induces the dimerization of the TLR4/MD-2 complex (PubMed: 19339971). This dimerization activates intracellular signaling pathways, such as MyD88 and TRIF, leading to the production of pro-inflammatory cytokines like TNF-alpha and IL-6 (NIH: PMC3101495). MD-2 is a significant therapeutic target for treating sepsis, where its overactivation leads to a cytokine storm (PubMed: 23835178). Drugs like Eritoran act as MD-2 antagonists by competing with LPS for the binding pocket, thereby preventing the inflammatory cascade (DrugBank: DB04873).

Other names

LY96Myeloid differentiation factor 2ESOP-1Protein MD-2

Antagonism of the lipopolysaccharide (LPS) binding site on MD-2 to prevent TLR4/MD-2 complex dimerization and downstream pro-inflammatory signaling (PubMed: 19339971).