Crystal structure of neurotoxin Ts1 from Tityus serrulatus provides insights into the specificity and toxicity of scorpion toxins.
The crystal structure of neurotoxin Ts1, a major component of the venom of the Brazilian scorpion Tityus serrulatus, has been determined at 1.7 A resolution. It is the first X-ray structure of a highly toxic anti-mammalian beta-toxin. The folding of the polypeptide chain of Ts1 is similar to that of other scorpion toxins. A cysteine-stabilised alpha-helix/beta-sheet motif forms the core of the flattened molecule. All residues identified as functionally important by chemical modification and site-directed mutagenesis are located on one side of the molecule, which is therefore considered as the Na+channel recognition site. The distribution of charged and non-polar residues over this surface determines the specificity of the toxin-channel interaction. Comparison to other scorpion toxins shows that positively charged groups at positions 1 and 12 as well as a negative charge at position 2 are likely determinants of the specificity of beta-toxins. In contrast, the contribution of the conserved aromatic cluster to the interaction might be relatively small. Comparison of Ts1 to weak beta-toxins from Centruroides sculpturatus Ewing reveals that a number of basic amino acid residues located on the face of the molecule opposite to the binding surface may account for the high toxicity of Ts1.
Polikarpov
I
I
Laboratório Nacional de Luz Síncrotron (LNLS), Campinas SP, CEP 13083-970, Brazil. igor@lnls.br
Junior
M S
MS
Marangoni
S
S
Toyama
M H
MH
Teplyakov
A
A
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019476:Insect Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D017386:Sequence Homology, Amino Acid
D019476:Insect Proteins; D009498:Neurotoxins; D012604:Scorpion Venoms; C120263:scorpion toxin Ts1, Tityus