6LFJ

Crystal structure of mouse DCAR2 CRD domain complex with IPM2

Summary for 6LFJ

• Entry DOI: 10.2210/pdb6lfj/pdb
• Related: 6KZR
• Descriptor: C-type lectin domain family 4, member b1, CALCIUM ION, 2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (6 entities in total)
• Functional Keywords: c-type lectin, sugar binding protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 33132.87

Authors

Omahdi, Z.,Horikawa, Y.,Toyonaga, K.,Kakuta, Y.,Yamasaki, S. (deposition date: 2019-12-03, release date: 2020-03-25, Last modification date: 2024-10-16)

Primary citation

Omahdi, Z.,Horikawa, Y.,Nagae, M.,Toyonaga, K.,Imamura, A.,Takato, K.,Teramoto, T.,Ishida, H.,Kakuta, Y.,Yamasaki, S.
Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR.
J.Biol.Chem., 295:5807-5817, 2020

PubMed Abstract: The C-type lectin receptors (CLRs) form a family of pattern recognition receptors 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 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 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or ), the CLR that binds phosphoglycolipids such as acylated phosphatidyl--inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala and Gln, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca-binding motif (Glu-Pro-Ser/EPS). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (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.

PubMed: 32139512
DOI: 10.1074/jbc.RA120.012491

Experimental method

X-RAY DIFFRACTION (1.84 Å)