GroEL as a molecular scaffold for structural analysis of the anthrax toxin pore

Nat Struct Mol Biol. 2008 Jul;15(7):754-60. doi: 10.1038/nsmb.1442. Epub 2008 Jun 22.

Abstract

We analyzed the 440-kDa transmembrane pore formed by the protective antigen (PA) moiety of anthrax toxin in the presence of GroEL by negative-stain electron microscopy. GroEL binds both the heptameric PA prepore and the PA pore. The latter interaction retards aggregation of the pore, prolonging its insertion-competent state. Two populations of unaggregated pores were visible: GroEL-bound pores and unbound pores. This allowed two virtually identical structures to be reconstructed, at 25-A and 28-A resolution, respectively. The structures were mushroom-shaped objects with a 125-A-diameter cap and a 100-A-long stem, consistent with earlier biochemical data. Thus, GroEL provides a platform for obtaining initial glimpses of a membrane protein structure in the absence of lipids or detergents and can function as a scaffold for higher-resolution structural analysis of the PA pore.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / ultrastructure
  • Bacterial Toxins / chemistry*
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / metabolism*
  • Chaperonin 60 / ultrastructure
  • Crystallography, X-Ray
  • Microscopy, Electron
  • Models, Molecular
  • Protein Binding / drug effects

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • Chaperonin 60
  • anthrax toxin
  • Adenosine Triphosphate