Mar 1, 2009 · The human immune system uses the TLR4-MD-2 complex to recognize the lipopolysaccharide (LPS) of Gram-negative bacteria, which cause diverse infections.

Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common 'pattern' in structurally diverse LPS molecules. To understand the ligand specificity and receptor activation mechanism of the TLR4-MD-2-LPS complex we determined its crystal structure.

Based on the binding mode of LPS to the TLR4-MD2 heterodimer, several strategies have been implemented to chemically modify lipid A structure, e.g., the removal of phosphate groups or a change in the position, number, or length of carbon chains or in the glucosamine backbone.

Dec 6, 2013 · In this review, we discuss the reported structures of the TLR4–MD-2 complex, LBP and CD14, and consider their implications for our understanding of TLR4–MD-2 activation in response to...

Mar 18, 2025 · The LPS-TLR4 immune response is a critical mechanism in the body's defense against Gram-negative bacterial infections, yet its dysregulation can lead to severe inflammatory diseases. ... MD-2, and TLR4-MD-2 complex and the binding pattern diagram of LPS and TLR4-MD2 complex. A LBP comprises two structural domains, each featuring antiparallel β ...

Jan 31, 2025 · Artesunate has been reported to inhibit the Toll-like receptor 4 (TLR4) pathway in macrophages after stimulation with lipopolysaccharide (LPS), which explains artesunate’s protective effect in...

MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as …

Oct 14, 2019 · The key residues of TLR4 and TLR4* identified by per-residue free energy decomposition (kcal/mol) in the TLR4/TLR4* interface of ligand-free (TLR4-MD2)2 tetramer, lipopolysaccharide (LPS)-bound (TLR4-MD2)2 tetramer, and neoseptin3-bound (TLR4-MD2)2 tetramer complexes.

Feb 17, 2020 · Myeloid differentiation protein-2 (MD2) contributes to ligand recognition and activation of TLRs in response to exogenous microbial insults or endogenous agents. We hypothesized that blocking MD2 using a specific inhibitor would prevent TLR4-mediated inflammatory responses and metastatic cancer growth.

The central findings from the current study provided strong evidence linking MD2-TLR4 to colon cancer growth: i) MD2 was upregulated in human colon cancer tissue, mouse colon cancer tissue in model of colitis-associated colon cancer, and colon cancer cell lines; ii) MD2 blockade prevented LPS-induced motility and invasiveness of colon cancer ...