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A Phenylalanine Clamp Catalyzes Protein Translocation Through the Anthrax Toxin Pore
Bryan A. Krantz,1*Roman A. Melnyk,1*Sen Zhang,1Stephen J. Juris,1D. Borden Lacy,1Zhengyan Wu,2Alan Finkelstein,2R. John Collier1
The protective antigen component of anthrax toxin forms a homoheptamericpore in the endosomal membrane, creating a narrow passagewayfor the enzymatic components of the toxin to enter the cytosol.We found that, during conversion of the heptameric precursorto the pore, the seven phenylalanine-427 residues convergedwithin the lumen, generating a radially symmetric heptad ofsolvent-exposed aromatic rings. This "-clamp" structure wasrequired for protein translocation and comprised the major conductance-blockingsite for hydrophobic drugs and model cations. We conclude thatthe clamp serves a chaperone-like function, interacting withhydrophobic sequences presented by the protein substrate asit 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.
To whom correspondence should be addressed. Email: jcollier{at}hms.harvard.edu
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[DOI: 10.1126/science.1116630] |Summary »|Full Text »|PDF »
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-clamp" structure was required for protein translocation and comprised the major conductance-blocking site for hydrophobic drugs and model cations. We conclude that the 
To whom correspondence should be addressed. Email: 
