Identification of an ion channel‐forming motif in the primary structure of tetanus and botulinum neurotoxins

FEBS Letters

Blewitt, Richard²  Montal, Mauricio²  Tomich, John M.¹  Monta, Myrta S.² 

[1] Departments of Pediatrics and Biochemistry, University of Southern California Medical School and Children's Hospital, Los Angeles, CA 90054-0700, USA;Department of Biology, University of California San Diego, La Jolla, CA 92093-0319, USA

关键词: Tetanus toxin;    Botulinum toxin;    Ionic channel;    Protein design;    Lipid bilayer;    Signal transduction;    TeTx;    tetanus toxin;    BoTxA;    botulinum neurotoxin serotype A;    PC;    1;    2-diphytanoyl-sn-glycero-3-phosphocholine;    τo;    open times;    τg;    closed times;   

DOI  :  10.1016/0014-5793(92)81173-J

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Synthetic peptides with amino acid sequences corresponding to predicted transmembrane segments of tetanus toxin were used as probes to identify a channel-forming motif. A peptide denoted TeTx II, with sequence GVVLLLEYIPEITLPVIAALSIA, forms cation-selective channels when reconstituted in planar lipid bilayers. The single channel conductance in 0.5 M NaCl or KCl is 28 ± 3 and 24 ± 2 pS, respectively. In contrast, a peptide with sequence NFIGALETTGVVLLLEYIPEIT, denoted as TeTx I. or a peptide with the same amino acid composition as TeTx II but with a randomized sequence, do not form channels. Conformational energy calculations show that a bundle of four amphipathic α-helices is a plausible structural motif underlying observable pore properties. The identified functional module may account for the channel-forming activity of both tetanus toxin and the homologous botulinum toxin A.

【 授权许可】

Unknown