3MHA

Crystal structure of LprG from Mycobacterium tuberculosis bound to PIM

Summary for 3MHA

• Entry DOI: 10.2210/pdb3mha/pdb
• Related: 3MH8 3MH9
• Descriptor: 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)
• Functional Keywords: lipoprotein, lprg, glycolipid binding protein, lipid binding protein, structural genomics, tb structural genomics consortium, tbsgc
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cell membrane; Lipid-anchor: P0A5I8
• Total number of polymer chains: 2
• Total formula weight: 44351.73

Authors

Tsai, H.-C.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2010-04-07, release date: 2010-09-01, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)