6lfj
From Proteopedia
Crystal structure of mouse DCAR2 CRD domain complex with IPM2
Structural highlights
FunctionPublication Abstract from PubMedThe C-type lectin receptors (CLRs) form a family of pattern recognition receptors (PRRs) that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca(2+) ion, allowing receptor interactions with sugar-containing ligands. Although well conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8-2.3 A resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR/Clec4b1), the only CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca(2+)-binding motif (Glu-Pro-Ser/EPS168-170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate di-mannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs. Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR.,Omahdi Z, Horikawa Y, Nagae M, Toyonaga K, Imamura A, Takato K, Teramoto T, Ishida H, Kakuta Y, Yamasaki S J Biol Chem. 2020 Mar 5. pii: RA120.012491. doi: 10.1074/jbc.RA120.012491. PMID:32139512[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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