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Science 29 July 2005:
Vol. 309. no. 5735, pp. 777 - 781
DOI: 10.1126/science.1113380
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Reports

A Phenylalanine Clamp Catalyzes Protein Translocation Through the Anthrax Toxin Pore

Bryan A. Krantz,1* Roman A. Melnyk,1* Sen Zhang,1 Stephen J. Juris,1 D. Borden Lacy,1 Zhengyan Wu,2 Alan Finkelstein,2 R. John Collier1{dagger}

The protective antigen component of anthrax toxin forms a homoheptameric pore in the endosomal membrane, creating a narrow passageway for the enzymatic components of the toxin to enter the cytosol. We found that, during conversion of the heptameric precursor to the pore, the seven phenylalanine-427 residues converged within the lumen, generating a radially symmetric heptad of solvent-exposed aromatic rings. This "{varphi}-clamp" structure was required for protein translocation and comprised the major conductance-blocking site for hydrophobic drugs and model cations. We conclude that the {varphi} clamp serves a chaperone-like function, interacting with hydrophobic sequences presented by the protein substrate as it unfolds during translocation.

1 Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. Email: jcollier{at}hms.harvard.edu

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