{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Walsh C"],"funding":["Medical Research Council","Wellcome Trust"],"pagination":["1245-54"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617842"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["181(2)"],"pubmed_abstract":["LPS signals through a membrane bound-complex of the lipid binding protein MD-2 and the receptor TLR4. In this study we identify discrete regions in both MD-2 and TLR4 that are required for signaling by lipid IVa, an LPS derivative that is an agonist in horse but an antagonist in humans. We show that changes in the electrostatic surface potential of both MD-2 and TLR4 are required in order that lipid IVa can induce signaling. In MD-2, replacing horse residues 57-66 and 82-89 with the equivalent human residues confers a level of constitutive activity on horse MD-2, suggesting that conformational switching in this protein is likely to be important in ligand-induced activation of MD-2/TLR4. We identify leucine-rich repeat 14 in the C terminus of TLR4 as essential for lipid IVa activation of MD"],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa."],"pmcid":["PMC7617842"],"funding_grant_id":["G1000133","G0400007","081744"],"pubmed_authors":["Walsh C","Maskell D","Smyth T","Gangloff M","Wei B","Monie T","McKinley TJ","Bryant C","Gay N"],"additional_accession":[]},"is_claimable":false,"name":"Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa.","description":"LPS signals through a membrane bound-complex of the lipid binding protein MD-2 and the receptor TLR4. In this study we identify discrete regions in both MD-2 and TLR4 that are required for signaling by lipid IVa, an LPS derivative that is an agonist in horse but an antagonist in humans. We show that changes in the electrostatic surface potential of both MD-2 and TLR4 are required in order that lipid IVa can induce signaling. In MD-2, replacing horse residues 57-66 and 82-89 with the equivalent human residues confers a level of constitutive activity on horse MD-2, suggesting that conformational switching in this protein is likely to be important in ligand-induced activation of MD-2/TLR4. We identify leucine-rich repeat 14 in the C terminus of TLR4 as essential for lipid IVa activation of MD","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Jul","modification":"2026-06-01T12:08:39.621Z","creation":"2026-04-08T12:05:52.493Z"},"accession":"S-EPMC7617842","cross_references":{"pubmed":["18606678"],"doi":["10.4049/jimmunol.181.2.1245"]}}