Biomaterial Database

Structural basis for plastic glycolipid recognition of the C-type lectin Mincle. 2023

Atsushi Furukawa, and Yusuke Shuchi, and Jiaqi Wang, and Pablo Adrian Guillen-Poza, and Shigenari Ishizuka, and Misuzu Kagoshima, and Risa Ikeno, and Hiroyuki Kumeta, and Sho Yamasaki, and Takanori Matsumaru, and Takashi Saitoh, and Katsumi Maenaka

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.

Mincle (macrophage-inducible C-type lectin, CLEC4E) is a C-type lectin immune-stimulatory receptor for cord factor, trehalose dimycolate (TDM), which serves as a potent component of adjuvants. The recognition of glycolipids by Mincle, especially their lipid parts, is poorly understood. Here, we performed nuclear magnetic resonance analysis, revealing that titration of trehalose harboring a linear short acyl chain showed a chemical shift perturbation of hydrophobic residues next to the Ca-binding site. Notably, there were split signals for Tyr201 upon complex formation, indicating two binding modes for the acyl chain. In addition, most Mincle residues close to the Ca-binding site showed no observable signals, suggesting their mobility on an ∼ ms scale even after complex formation. Mutagenesis study supported two putative lipid-binding modes for branched acyl-chain TDM binding. These results provide novel insights into the plastic-binding modes of Mincle toward a wide range of glycol- and glycerol-lipids, important for rational adjuvant development.

UI	MeSH Term	Description	Entries
D003311	Cord Factors	Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals.	Trehalose Dimycolates,Cord Factor,Trehalose-6,6'-Dimycolate,Dimycolates, Trehalose,Factor, Cord,Factors, Cord,Trehalose 6,6' Dimycolate
D006017	Glycolipids	Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)	Glycolipid
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D016296	Mutagenesis	Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.	Mutageneses
D037181	Lectins, C-Type	A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.	C-Type Lectin Receptor,C-Type Lectins,C-Type Lectin,Lectin, C-Type,Receptors, C-Type Lectin,C Type Lectin,C Type Lectin Receptor,C Type Lectins,C-Type Lectin Receptors,Lectin Receptor, C-Type,Lectin Receptors, C-Type,Lectin, C Type,Lectins, C Type,Receptor, C-Type Lectin,Receptors, C Type Lectin