3MTX

Crystal structure of chicken MD-1

Summary for 3MTX

• Entry DOI: 10.2210/pdb3mtx/pdb
• Related: 3MU3
• Descriptor: Protein MD-1, (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE, TRIETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: md-1, ly86, rp105 associated protein, immune system
• Biological source: Gallus gallus (bantam,chickens)
• Cellular location: Secreted, extracellular space (By similarity): Q90890
• Total number of polymer chains: 2
• Total formula weight: 35893.13

Authors

Yoon, S.I.,Hong, M.,Han, G.W.,Wilson, I.A. (deposition date: 2010-05-01, release date: 2010-06-09, Last modification date: 2024-10-16)

Primary citation

Yoon, S.I.,Hong, M.,Han, G.W.,Wilson, I.A.
Crystal structure of soluble MD-1 and its interaction with lipid IVa.
Proc.Natl.Acad.Sci.USA, 107:10990-10995, 2010

PubMed Abstract: Lipopolysaccharide (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.

PubMed: 20534476
DOI: 10.1073/pnas.1004153107

Experimental method

X-RAY DIFFRACTION (2 Å)