Regardless of overall close structural and functional similarity, human (h) and murine (m) MD-2 show several species-related differences, including the ability of hMD-2, but not mMD-2, to bind LPS in the absence of TLR4. Wild-type mMD-2 can support TLR4-dependent cell activation by LPS only when mMD-2 and mTLR4 are coexpressed in the same cell. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine functional differences between soluble h and mMD-2. A relatively minute change of valine to alanine at amino acid 135 of hMD-2 surprisingly completely abolished LPS binding to soluble MD-2, converting the humane cellular response to murine-like response.
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COBISS.SI-ID: 36955909