A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore.

Krantz BA, Melnyk RA, Zhang S, Juris SJ, Lacy DB, Wu Z, Finkelstein A, Collier RJ
Science. 2005 309 (5735): 777-81

PMID: 16051798 · PMCID: PMC1815389 · DOI:10.1126/science.1113380

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 "phi-clamp" structure was required for protein translocation and comprised the major conductance-blocking site for hydrophobic drugs and model cations. We conclude that the phi clamp serves a chaperone-like function, interacting with hydrophobic sequences presented by the protein substrate as it unfolds during translocation.

MeSH Terms (23)

Amino Acid Sequence Amino Acid Substitution Antigens, Bacterial Bacillus anthracis Bacterial Toxins Binding Sites Cell Membrane Cytosol Electron Spin Resonance Spectroscopy Endosomes Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Lipid Bilayers Models, Biological Models, Molecular Molecular Sequence Data Mutagenesis Onium Compounds Organophosphorus Compounds Phenylalanine Protein Conformation Protein Folding Quaternary Ammonium Compounds

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