4TW1

Crystal structure of the octameric pore complex of the Staphylococcus aureus Bi-component Toxin LukGH


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Structure-Function Analysis of Heterodimer Formation, Oligomerization, and Receptor Binding of the Staphylococcus aureus Bi-component Toxin LukGH.

Badarau, A.Rouha, H.Malafa, S.Logan, D.T.Hakansson, M.Stulik, L.Dolezilkova, I.Teubenbacher, A.Gross, K.Maierhofer, B.Weber, S.Jagerhofer, M.Hoffman, D.Nagy, E.

(2015) J Biol Chem 290: 142-156

  • DOI: https://doi.org/10.1074/jbc.M114.598110
  • Primary Citation of Related Structures:  
    4TW1

  • PubMed Abstract: 

    The bi-component leukocidins of Staphylococcus aureus are important virulence factors that lyse human phagocytic cells and contribute to immune evasion. The γ-hemolysins (HlgAB and HlgCB) and Panton-Valentine leukocidin (PVL or LukSF) were shown to assemble from soluble subunits into membrane-bound oligomers on the surface of target cells, creating barrel-like pore structures that lead to cell lysis. LukGH is the most distantly related member of this toxin family, sharing only 30-40% amino acid sequence identity with the others. We observed that, unlike other leukocidin subunits, recombinant LukH and LukG had low solubility and were unable to bind to target cells, unless both components were present. Using biolayer interferometry and intrinsic tryptophan fluorescence we detected binding of LukH to LukG in solution with an affinity in the low nanomolar range and dynamic light scattering measurements confirmed formation of a heterodimer. We elucidated the structure of LukGH by x-ray crystallography at 2.8-Å resolution. This revealed an octameric structure that strongly resembles that reported for HlgAB, but with important structural differences. Structure guided mutagenesis studies demonstrated that three salt bridges, not found in other bi-component leukocidins, are essential for dimer formation in solution and receptor binding. We detected weak binding of LukH, but not LukG, to the cellular receptor CD11b by biolayer interferometry, suggesting that in common with other members of this toxin family, the S-component has the primary contact role with the receptor. These new insights provide the basis for novel strategies to counteract this powerful toxin and Staphylococcus aureus pathogenesis.


  • Organizational Affiliation

    From Arsanis Biosciences, Vienna Biocenter Campus, Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Possible leukocidin subunit
A, C, E, G, I
A, C, E, G, I, K, M, O
311Staphylococcus aureus subsp. aureus USA300_TCH1516Mutation(s): 0 
Gene Names: USA300HOU_2011
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Possible leukocidin subunit
B, D, F, H, J
B, D, F, H, J, L, N, P
324Staphylococcus aureus subsp. aureus USA300_TCH1516Mutation(s): 0 
Gene Names: USA300HOU_2013
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135.497α = 90
b = 198.558β = 103.26
c = 179.535γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
SCALAdata scaling
PDB_EXTRACTdata extraction
PHASERphasing
REFMACrefinement
XSCALEdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-11-12
    Type: Initial release
  • Version 1.1: 2014-11-19
    Changes: Database references
  • Version 1.2: 2015-01-14
    Changes: Database references
  • Version 1.3: 2015-04-08
    Changes: Derived calculations
  • Version 1.4: 2018-01-17
    Changes: Data collection
  • Version 1.5: 2019-06-12
    Changes: Data collection, Structure summary
  • Version 1.6: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Refinement description