You are here
Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.
Title | Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Drage, MG, Tsai, H-C, Pecora, ND, Cheng, T-Y, Arida, AR, Shukla, S, Rojas, RE, Seshadri, C, D Moody, B, W Boom, H, Sacchettini, JC, Harding, CV |
Journal | Nat Struct Mol Biol |
Volume | 17 |
Issue | 9 |
Pagination | 1088-95 |
Date Published | 2010 Sep |
ISSN | 1545-9985 |
Keywords | Acylation, Bacterial Proteins, Cell Line, Glycolipids, Humans, Lipopolysaccharides, Lipoproteins, Models, Molecular, Mutation, Mycobacterium tuberculosis, Phosphatidylinositols, Protein Binding, Protein Structure, Tertiary, Toll-Like Receptor 2 |
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. |
DOI | 10.1038/nsmb.1869 |
Alternate Journal | Nat. Struct. Mol. Biol. |
PubMed ID | 20694006 |
PubMed Central ID | PMC2933325 |
Grant List | AI027243 / AI / NIAID NIH HHS / United States AI034343 / AI / NIAID NIH HHS / United States AI035726 / AI / NIAID NIH HHS / United States AI049313 / AI / NIAID NIH HHS / United States AI067093 / AI / NIAID NIH HHS / United States AI068135 / AI / NIAID NIH HHS / United States AI069085 / AI / NIAID NIH HHS / United States AI071155 / AI / NIAID NIH HHS / United States HL055967 / HL / NHLBI NIH HHS / United States P01 AI068135 / AI / NIAID NIH HHS / United States P01 AI068135-05 / AI / NIAID NIH HHS / United States T32 AI007061 / AI / NIAID NIH HHS / United States |