MD-2 protein is essential for identification of bacterial endotoxin, as it directly binds LPS. This protein is also responsible for differences in response to bacterial infection between different species. We investigated the differences in the response to LPS between mouse and human where we found two key positions that significanrly affect the response to LPS. This finding helps to understand differences in response to LPS and susceptibility to sepsis among different species.
COBISS.SI-ID: 4227098
TLR4 receptor recognizes bacterial toxin LPS and is one of the most researched receptors, which plays an important role in many physiological processes. So far, the molecular mechanism of activation of this receptor has not yet been known. The above mentioned model representsnew paradigm of recognition and is important for devising new inhibitors and activation of TLR4.
COBISS.SI-ID: 4120602
TLR4/MD-2 complex recognizes bacterial endotoxin and is essential in other inflammatory diseases. Pharmacological inhibitionIt is therefore very important for the therapeutic use. We found that MD-2 represents the most suitable target and discovered the possibility of the free cysteine residue at position 133 of MD-2. We have shown the binding and inhibition of 4 commercially available compounds and demonstrated a reduction of the production of pro-inflammatory TNFa in a mouse model using JTT-755. The results represent a completely new type of effective anti-TLR4 compounds.
COBISS.SI-ID: 4173082
TLRs are type I transmembrane proteins. Up to now we only had structural information or models of separate domains of TLRs and much less on their required flexibility. Insertion of a linker between the transmembrane and ectodomain or within the ectodomain decreased activation. This suggests the requirement for tight coupling of the ectodomain to the membrane, which may facilitate its interaction with ligand, promote dimerization and prevent interaction with the cell-membrane surface.
COBISS.SI-ID: 4118298
In certain cases, anti-idiotypic antibodies that recognize an antigen-combining site of an antibody can mimic the structure and/or function of certain antigens. We used an anti-idiotype approach, with the aim of evoking antibody response against the pathological isoform of the prion protein (PrPSc). Our results demonstrate that it is possible to induce a strong anti-idiotypic immune response against the V5B2 monoclonal antibody. We conclude that selected antibodies bind to the antigen-combining site of the V5B2 monoclonal antibody and might even resemble the PrPSc-specific epitope.
COBISS.SI-ID: 2440072