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]
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]
Kato K, Morrison AM, Nakano T, Tashiro K, Honjo T (July 2000). "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and reproductive systems of embryonic and adult mice". Blood. 96 (1): 362–4.
doi:
10.1182/blood.V96.1.362.
PMID10891475.
Jia HP, Kline JN, Penisten A, Apicella MA, Gioannini TL, Weiss J, et al. (August 2004). "Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2". American Journal of Physiology. Lung Cellular and Molecular Physiology. 287 (2): L428-37.
doi:
10.1152/ajplung.00377.2003.
PMID15121639.
S2CID13203884.
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]
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]
Kato K, Morrison AM, Nakano T, Tashiro K, Honjo T (July 2000). "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and reproductive systems of embryonic and adult mice". Blood. 96 (1): 362–4.
doi:
10.1182/blood.V96.1.362.
PMID10891475.
Jia HP, Kline JN, Penisten A, Apicella MA, Gioannini TL, Weiss J, et al. (August 2004). "Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2". American Journal of Physiology. Lung Cellular and Molecular Physiology. 287 (2): L428-37.
doi:
10.1152/ajplung.00377.2003.
PMID15121639.
S2CID13203884.