A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore.
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.
Krantz
Bryan A
BA
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Melnyk
Roman A
RA
Zhang
Sen
S
Juris
Stephen J
SJ
Lacy
D Borden
DB
Wu
Zhengyan
Z
Finkelstein
Alan
A
Collier
R John
RJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001408:Bacillus anthracis / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D011992:Endosomes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010649:Phenylalanine / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D000644:Quaternary Ammonium Compounds / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008051:Lipid Bilayers; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; C030325:anthrax toxin; D010649:Phenylalanine; C009405:tetrabutylammonium; C013289:tetraphenylphosphonium