3MH9

Crystal structure of LprG mutant V91W from Mycobacterium tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.79 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.

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.

(2010) Nat Struct Mol Biol 17: 1088-1095

  • DOI: https://doi.org/10.1038/nsmb.1869
  • Primary Citation of Related Structures:  
    3MH8, 3MH9, 3MHA

  • 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.


  • Organizational Affiliation

    Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lipoprotein lprGA [auth C],
B [auth A]
218Mycobacterium tuberculosis H37RvMutation(s): 1 
Gene Names: lpp-27lprGMT1455MTCY21B4.28cRv1411c
Membrane Entity: Yes 
UniProt
Find proteins for P9WK45 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WK45 
Go to UniProtKB:  P9WK45
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WK45
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.79 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.726α = 90
b = 55.973β = 99.55
c = 96.936γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-06
    Changes: Database references
  • Version 1.3: 2024-02-21
    Changes: Data collection