8HB5

Crystal structure of Mincle in complex with HD-275

8HB5 の概要

• エントリーDOI: 10.2210/pdb8hb5/pdb
• 分子名称: 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)
• 機能のキーワード: innate immunity, c-type lectin receptors, mycobacterium leprae, immune system
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17757.94

構造登録者

Ishizuka, S.,Nagae, M.,Yamasaki, S. (登録日: 2022-10-27, 公開日: 2023-08-09, 最終更新日: 2024-11-06)

主引用文献

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

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: 37521780
DOI: 10.1021/acscentsci.3c00040

実験手法

X-RAY DIFFRACTION (2.6 Å)