Recombinant MD2 protein (Active)

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MD2 also known as lymphocyte antigen 96 is a small glycoprotein with a mass of approximately 18 kDa. It is mainly found in myeloid cells including monocytes and macrophages where it plays an important role in immune response. MD2 serves as a co-receptor working closely with Toll-like receptor 4 (TLR4) to facilitate the recognition of bacterial lipopolysaccharides (LPS) the components of the outer membrane of Gram-negative bacteria. The interaction between MD2 and TLR4 is important for the initiation of downstream signaling that activates the immune system.

Biological function summary

MD2 acts as an integral part of the Toll-like receptor complex specifically the TLR4/MD2 complex. This complex recognizes pathogen-associated molecular patterns (PAMPs) found on microbes triggering the activation of innate immune responses. By binding to LPS MD2 undergoes a conformational change that enables TLR4 dimerization and subsequent recruitment of adapter proteins like MyD88 and TRIF. This recruitment leads to the activation of NF-kB and MAPK signaling pathways which promote the transcription of pro-inflammatory cytokines essential for an adequate immune response.

Pathways

MD2 and its associated TLR4 are central components of the innate immune signaling cascade. They contribute to the MyD88-dependent and TRIF-dependent pathways both pivotal to inflammation and immune defense. These pathways orchestrate a range of immune responses by mediating the production of cytokines and type I interferons respectively. MD2 also interacts with other proteins such as CD14 which increases the sensitivity of the TLR4/MD2 complex to LPS enhancing its ability to respond to bacterial invasion.

Alterations in MD2-mediated signaling are associated with sepsis and inflammatory diseases like rheumatoid arthritis. MD2/TLR4 interaction plays a pivotal role in the hyperinflammatory response observed during sepsis where excessive cytokine release can lead to tissue damage and organ failure. In rheumatoid arthritis MD2-related signaling contributes to chronic inflammation and joint destruction. Drugs targeting the MD2-TLR4 pathway are under investigation for managing these conditions revealing the critical role of MD2 in these disease mechanisms.