3mu3
Crystal structure of chicken MD-1 complexed with lipid IVaCrystal structure of chicken MD-1 complexed with lipid IVa
Structural highlights
Function[LY86_CHICK] May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production. Important for efficient CD180 cell surface expression (By similarity). Evolutionary Conservation![]() Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLipopolysaccharide (LPS) of Gram-negative bacteria is a common pathogen-associated molecular pattern (PAMP) that induces potent innate immune responses. The host immune response against LPS is triggered by myeloid differentiation factor 2 (MD-2) in association with Toll-like receptor 4 (TLR4) on the cell surface. The MD-2/TLR4-mediated LPS response is regulated by the evolutionarily related complex of MD-1 and Toll-like receptor homolog RP105. Here, we report crystallographic and biophysical data that demonstrate a previously unidentified direct interaction of MD-1 with LPS. The crystal structure of chicken MD-1 (cMD-1) at 2.0 A resolution exhibits a beta-cup-like fold, similar to MD-2, that encloses a hydrophobic cavity between the two beta-sheets. A lipid-like moiety was observed inside the cavity, suggesting the possibility of a direct MD-1/LPS interaction. LPS was subsequently identified as an MD-1 ligand by native gel electrophoresis and gel filtration analyses. The crystal structure of cMD-1 with lipid IVa, an LPS precursor, at 2.4 A resolution revealed that the lipid inserts into the deep hydrophobic cavity of the beta-cup-like structure, but with some important differences compared with MD-2. These findings suggest that soluble MD-1 alone, in addition to its complex with RP105, can regulate host LPS sensitivity. Crystal structure of soluble MD-1 and its interaction with lipid IVa.,Yoon SI, Hong M, Han GW, Wilson IA Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10990-5. Epub 2010 Jun 1. PMID:20534476[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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