3MHA

Crystal structure of LprG from Mycobacterium tuberculosis bound to PIM

3MHA の概要

• エントリーDOI: 10.2210/pdb3mha/pdb
• 関連するPDBエントリー: 3MH8 3MH9
• 分子名称: Lipoprotein lprG, (1S,2R,3R,4S,5R,6S)-2-(alpha-L-allopyranosyloxy)-3,4,5-trihydroxy-6-({6-O-[(1R)-1-hydroxyhexadecyl]-beta-L-gulopyranosyl}oxy)cyclohexyl (2R)-2-{[(1S)-1-hydroxyhexadecyl]oxy}-3-{[(1S,10S)-1-hydroxy-10-methyloctadecyl]oxy}propyl hydrogen (R)-phosphate (3 entities in total)
• 機能のキーワード: lipoprotein, lprg, glycolipid binding protein, lipid binding protein, structural genomics, tb structural genomics consortium, tbsgc
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cell membrane; Lipid-anchor: P0A5I8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44351.73

構造登録者

Tsai, H.-C.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (登録日: 2010-04-07, 公開日: 2010-09-01, 最終更新日: 2023-09-06)

主引用文献

Drage, M.G.,Tsai, H.C.,Pecora, N.D.,Cheng, T.Y.,Arida, A.R.,Shukla, S.,Rojas, R.E.,Seshadri, C.,Moody, D.B.,Boom, W.H.,Sacchettini, J.C.,Harding, C.V.
Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.
Nat.Struct.Mol.Biol., 17:1088-1095, 2010

PubMed Abstract: Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a glycolipid binding function of LprG that enhances recognition of triacylated MTB glycolipids by TLR2 and may affect glycolipid assembly or transport for bacterial cell wall biogenesis.

PubMed: 20694006
DOI: 10.1038/nsmb.1869

実験手法

X-RAY DIFFRACTION (1.85 Å)