skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of 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.

Authors:
; ; ; ; ; ; ; ; ; ; ;  [1]
  1. Case Western
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002721
Resource Type:
Journal Article
Journal Name:
Nat. Struct. Mol. Biol.
Additional Journal Information:
Journal Volume: 17; Journal Issue: (9) ; 09, 2010
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; CELL WALL; CHAINS; CRYSTAL STRUCTURE; GLYCOLIPIDS; LIPOPROTEINS; MICE; MYCOBACTERIUM TUBERCULOSIS; TRANSPORT; VIRULENCE

Citation Formats

Drage, Michael G, Tsai, Han-Chun, Pecora, Nicole D, Cheng, Tan-Yun, Arida, Ahmad R, Shukla, Supriya, Rojas, Roxana E, Seshadri, Chetan, Moody, D Branch, Boom, W Henry, Sacchettini, James C, Harding, Clifford V, BWH), and TAM). Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2. United States: N. p., 2010. Web. doi:10.1038/nsmb.1869.
Drage, Michael G, Tsai, Han-Chun, Pecora, Nicole D, Cheng, Tan-Yun, Arida, Ahmad R, Shukla, Supriya, Rojas, Roxana E, Seshadri, Chetan, Moody, D Branch, Boom, W Henry, Sacchettini, James C, Harding, Clifford V, BWH), & TAM). Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2. United States. https://doi.org/10.1038/nsmb.1869
Drage, Michael G, Tsai, Han-Chun, Pecora, Nicole D, Cheng, Tan-Yun, Arida, Ahmad R, Shukla, Supriya, Rojas, Roxana E, Seshadri, Chetan, Moody, D Branch, Boom, W Henry, Sacchettini, James C, Harding, Clifford V, BWH), and TAM). 2010. "Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2". United States. https://doi.org/10.1038/nsmb.1869.
@article{osti_1002721,
title = {Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2},
author = {Drage, Michael G and Tsai, Han-Chun and Pecora, Nicole D and Cheng, Tan-Yun and Arida, Ahmad R and Shukla, Supriya and Rojas, Roxana E and Seshadri, Chetan and Moody, D Branch and Boom, W Henry and Sacchettini, James C and Harding, Clifford V and BWH) and TAM)},
abstractNote = {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},
url = {https://www.osti.gov/biblio/1002721}, journal = {Nat. Struct. Mol. Biol.},
number = (9) ; 09, 2010,
volume = 17,
place = {United States},
year = {Mon Sep 27 00:00:00 EDT 2010},
month = {Mon Sep 27 00:00:00 EDT 2010}
}