New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing

• Published in: The Journal of biological chemistry Vol. 287; no. 15; pp. 12321 - 12330
• Main Authors: Saucedo, Alma Leticia, Flores-Solis, David, Rodríguez de la Vega, Ricardo C, Ramírez-Cordero, Belén, Hernández-López, Rogelio, Cano-Sánchez, Patricia, Noriega Navarro, Roxana, García-Valdés, Jesús, Coronas-Valderrama, Fredy, de Roodt, Adolfo, Brieba, Luis G, Domingos Possani, Lourival, del Río-Portilla, Federico
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 06-04-2012
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Cysteine - chemistry; Membrane Potentials - drug effects; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Protein Structure and Folding; Protein Structure, Tertiary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - pharmacology; Scorpion Venoms - chemistry; Scorpion Venoms - isolation & purification; Scorpion Venoms - pharmacology; Scorpions; Sequence Analysis, Protein; Structural Homology, Protein; Surface Properties; Xenopus
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.329607

Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded β-sheet, conforming a cystine-stabilized α/β scaffold (CSα/β). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/β scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.