Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore.
BACKGROUND
A key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the Protective Antigen (PA) moiety. Formation of this transmembrane pore by PA involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel.


RESULTS
We examined the effects on pore formation, protein translocation, and cytotoxicity, of mutating two phenylalanines, F313 and F314, that lie at the tip the beta barrel, and a third one, F324, that lies part way up the barrel.


CONCLUSIONS
Our results show that the function of these phenylalanine residues is to mediate membrane insertion and formation of stable transmembrane channels. Unlike F427, a key luminal residue in the cap of the pore, F313, F314, and F324 do not directly affect protein translocation through the pore. Our findings add to our knowledge of structure-function relationships of a key virulence factor of the anthrax bacillus.
Wang
Jie
J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Vernier
Gregory
G
Fischer
Audrey
A
Collier
R John
RJ
D000942:Antigens, Bacterial / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry*; D010649:Phenylalanine / Q000502:physiology*; D011487:Protein Conformation
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D010649:Phenylalanine