Myeloid differentiation protein 2 (MD-2)

Myeloid differentiation protein 2 (MD-2) is a secreted accessory protein encoded by the LY96 gene that is essential for the innate immune response to Gram-negative bacteria. MD-2 associates with Toll-like receptor 4 (TLR4) on the cell surface, where it binds lipopolysaccharide (LPS) from bacterial membranes and enables TLR4-mediated signaling. This interaction is fundamental for recognizing bacterial components and activating downstream pro-inflammatory pathways, including NF-κB. Structurally, MD-2 possesses a β-cup fold with a hydrophobic pocket for LPS and related ligands. MD-2 has roles in various diseases involving inflammation, cardiovascular dysfunction, and cancer progression (notably prostate cancer), and its inhibition reduces pathological inflammation and metastasis in animal models. MD-2 is being explored as a therapeutic target for anti-inflammatory and anti-metastatic drugs, and serum MD-2 may serve as a biomarker for disease activity and prognosis[1][2][3][4][5][6][7].

Other names

Lymphocyte antigen 96LY96Myeloid differentiation factor 2

Inhibition of TLR4/MD-2 interaction blocks LPS-induced signaling and inflammation; Modulation of MD-2 binding pocket alters TLR4 dimerization and downstream pathway activation