2Q97

Complex of mammalian actin with toxofilin from toxoplasma gondii


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer

Lee, S.H.Hayes, D.B.Rebowski, G.Tardieux, I.Dominguez, R.

(2007) Proc Natl Acad Sci U S A 104: 16122-16127

  • DOI: https://doi.org/10.1073/pnas.0705794104
  • Primary Citation of Related Structures:  
    2Q97

  • PubMed Abstract: 

    Many human pathogens exploit the actin cytoskeleton during infection, including Toxoplasma gondii, an apicomplexan parasite related to Plasmodium, the agent of malaria. One of the most abundantly expressed proteins of T. gondii is toxofilin, a monomeric actin-binding protein (ABP) involved in invasion. Toxofilin is found in rhoptry and presents an N-terminal signal sequence, consistent with its being secreted during invasion. We report the structure of toxofilin amino acids 69-196 in complex with the host mammalian actin. Toxofilin presents an extended conformation and interacts with an antiparallel actin dimer, in which one of the actins is related by crystal symmetry. Consistent with this observation, analytical ultracentrifugation analysis shows that toxofilin binds two actins in solution. Toxofilin folds into five consecutive helices, which form three relatively independent actin-binding sites. Helices 1 and 2 bind the symmetry-related actin molecule and cover its nucleotide-binding cleft. Helices 3-5 bind the other actin and constitute the primary actin-binding region. Helix 3 interacts in the cleft between subdomains 1 and 3, a common binding site for most ABPs. Helices 4 and 5 wrap around actin subdomain 4, and residue Gln-134 of helix 4 makes a hydrogen-bonding contact with the nucleotide in actin, both of which are unique features among ABPs. Toxofilin dramatically inhibits nucleotide exchange on two actin molecules simultaneously. This effect is linked to the formation of the antiparallel actin dimer because a construct lacking helices 1 and 2 binds only one actin and inhibits nucleotide exchange less potently.


  • Organizational Affiliation

    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Actin, alpha skeletal muscle375Oryctolagus cuniculusMutation(s): 0 
UniProt
Find proteins for P68135 (Oryctolagus cuniculus)
Explore P68135 
Go to UniProtKB:  P68135
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68135
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ToxofilinB [auth T]129Toxoplasma gondiiMutation(s): 0 
Gene Names: toxofilin
UniProt
Find proteins for Q9NG25 (Toxoplasma gondii)
Explore Q9NG25 
Go to UniProtKB:  Q9NG25
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NG25
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
D [auth A]ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
C [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
HIC
Query on HIC
A
L-PEPTIDE LINKINGC7 H11 N3 O2HIS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 
  • Space Group: P 41 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.523α = 90
b = 54.523β = 90
c = 363.1γ = 90
Software Package:
Software NamePurpose
AMoREphasing
REFMACrefinement
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: 2007-10-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-24
    Changes: Atomic model
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description