2WCD

Crystal structure of the assembled cytolysin A pore


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.29 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Structure of a Cytolytic Alpha-Helical Toxin Pore Reveals its Assembly Mechanism

Mueller, M.Grauschopf, U.Maier, T.Glockshuber, R.Ban, N.

(2009) Nature 459: 726

  • DOI: https://doi.org/10.1038/nature08026
  • Primary Citation of Related Structures:  
    2WCD

  • PubMed Abstract: 

    Pore-forming toxins (PFTs) are a class of potent virulence factors that convert from a soluble form to a membrane-integrated pore. They exhibit their toxic effect either by destruction of the membrane permeability barrier or by delivery of toxic components through the pores. Among the group of bacterial PFTs are some of the most dangerous toxins, such as diphtheria and anthrax toxin. Examples of eukaryotic PFTs are perforin and the membrane-attack complex, proteins of the immune system. PFTs can be subdivided into two classes, alpha-PFTs and beta-PFTs, depending on the suspected mode of membrane integration, either by alpha-helical or beta-sheet elements. The only high-resolution structure of a transmembrane PFT pore is available for a beta-PFT--alpha-haemolysin from Staphylococcus aureus. Cytolysin A (ClyA, also known as HlyE), an alpha-PFT, is a cytolytic -helical toxin responsible for the haemolytic phenotype of several Escherichia coli and Salmonella enterica strains. ClyA is cytotoxic towards cultured mammalian cells, induces apoptosis of macrophages and promotes tissue pervasion. Electron microscopic reconstructions demonstrated that the soluble monomer of ClyA must undergo large conformational changes to form the transmembrane pore. Here we report the 3.3 A crystal structure of the 400 kDa dodecameric transmembrane pore formed by ClyA. The tertiary structure of ClyA protomers in the pore is substantially different from that in the soluble monomer. The conversion involves more than half of all residues. It results in large rearrangements, up to 140 A, of parts of the monomer, reorganization of the hydrophobic core, and transitions of -sheets and loop regions to -helices. The large extent of interdependent conformational changes indicates a sequential mechanism for membrane insertion and pore formation.


  • Organizational Affiliation

    Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEMOLYSIN E, CHROMOSOMAL
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X
309Escherichia coli K-12Mutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P77335 (Escherichia coli (strain K12))
Explore P77335 
Go to UniProtKB:  P77335
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP77335
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EMC
Query on EMC

Download Ideal Coordinates CCD File 
AA [auth B]
AB [auth O]
BA [auth B]
BB [auth O]
CA [auth C]
AA [auth B],
AB [auth O],
BA [auth B],
BB [auth O],
CA [auth C],
CB [auth P],
DA [auth C],
DB [auth P],
EA [auth D],
EB [auth Q],
FA [auth D],
FB [auth Q],
GA [auth E],
GB [auth R],
HA [auth E],
HB [auth R],
IA [auth F],
IB [auth S],
JA [auth F],
JB [auth S],
KA [auth G],
KB [auth T],
LA [auth G],
LB [auth T],
MA [auth H],
MB [auth U],
NA [auth H],
NB [auth U],
OA [auth I],
OB [auth V],
PA [auth I],
PB [auth V],
QA [auth J],
QB [auth W],
RA [auth J],
RB [auth W],
SA [auth K],
SB [auth X],
TA [auth K],
TB [auth X],
UA [auth L],
VA [auth L],
WA [auth M],
XA [auth M],
Y [auth A],
YA [auth N],
Z [auth A],
ZA [auth N]
ETHYL MERCURY ION
C2 H5 Hg
MJOUBOKSWBMNGQ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.29 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.43α = 94.44
b = 114.41β = 85.92
c = 270.55γ = 102.55
Software Package:
Software NamePurpose
XDSdata reduction
SCALAdata scaling
SHELXDphasing
SHARPphasing
PHENIXrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-05-05
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance