title: Comparison of the pH-induced conformational change of different clostridial neurotoxins.
abstract: Clostridial neurotoxins are internalized inside acidic compartments, wherefrom the catalytic chain translocates across the membrane into the cytosol in a low pH-driven process, reaching its proteolytic substrates. The pH range in which the structural rearrangement of clostridial neurotoxins takes place was determined by 8-anilinonaphthalene-1-sulfonate and tryptophan fluorescence measurements. Half conformational change was attained at pH 4.55, 4.50, 4.40, 4.60, 4.40, and 4.40 for tetanus neurotoxin and botulinum neurotoxin serotypes /A, /B, /C, /E, and /F, respectively. This similarity indicates the key residues for the conformation transition are strongly conserved. Acidic liposomes support the conformational rearrangement shifting the effect versus higher pH values, whereas zwitterionic liposomes do not. The disulfide bridge linking the light and the heavy chains together needs to be oxidized to allow toxin membrane insertion, indicating that in vivo its reduction follows exposure to the cytosol after penetration of the endosomal membrane.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, I-35121 Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Puhar
authors.forename: E A
authors.initials: EA
authors.lastname: Johnson
authors.forename: O
authors.initials: O
authors.lastname: Rossetto
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000494:pharmacology; D001427:Bacterial Toxins / Q000737:chemistry*; D003013:Clostridium / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D009498:Neurotoxins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013744:Tetanus Toxin / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D000817:Anilino Naphthalenesulfonates; D001427:Bacterial Toxins; D008081:Liposomes; D009498:Neurotoxins; D010455:Peptides; D013744:Tetanus Toxin; C027132:1-anilino-8-naphthalenesulfonate; D014364:Tryptophan