8HB5
Crystal structure of Mincle in complex with HD-275
Summary for 8HB5
| Entry DOI | 10.2210/pdb8hb5/pdb |
| Descriptor | C-type lectin domain family 4 member E, CALCIUM ION, (2~{R},3~{R},4~{S},5~{S},6~{R})-6-(methoxymethyl)oxane-2,3,4,5-tetrol, ... (4 entities in total) |
| Functional Keywords | innate immunity, c-type lectin receptors, mycobacterium leprae, immune system |
| Biological source | Bos taurus (cattle) |
| Total number of polymer chains | 1 |
| Total formula weight | 17757.94 |
| Authors | Ishizuka, S.,Nagae, M.,Yamasaki, S. (deposition date: 2022-10-27, release date: 2023-08-09, Last modification date: 2024-11-06) |
| Primary citation | Ishizuka, S.,van Dijk, J.H.M.,Kawakita, T.,Miyamoto, Y.,Maeda, Y.,Goto, M.,Le Calvez, G.,Groot, L.M.,Witte, M.D.,Minnaard, A.J.,van der Marel, G.A.,Ato, M.,Nagae, M.,Codee, J.D.C.,Yamasaki, S. PGL-III, a Rare Intermediate of Mycobacterium leprae Phenolic Glycolipid Biosynthesis, Is a Potent Mincle Ligand. Acs Cent.Sci., 9:1388-1399, 2023 Cited by PubMed Abstract: Although leprosy (Hansen's disease) is one of the oldest known diseases, the pathogenicity of () remains enigmatic. Indeed, the cell wall components responsible for the immune response against are as yet largely unidentified. We reveal here phenolic glycolipid-III (PGL-III) as an -specific ligand for the immune receptor Mincle. PGL-III is a scarcely present trisaccharide intermediate in the biosynthetic pathway to PGL-I, an abundant and characteristic glycolipid. Using activity-based purification, we identified PGL-III as a Mincle ligand that is more potent than the well-known trehalose dimycolate. The cocrystal structure of Mincle and a synthetic PGL-III analogue revealed a unique recognition mode, implying that it can engage multiple Mincle molecules. In Mincle-deficient mice infected with , increased bacterial burden with gross pathologies were observed. These results show that PGL-III is a noncanonical ligand recognized by Mincle, triggering protective immunity. PubMed: 37521780DOI: 10.1021/acscentsci.3c00040 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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