New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing |
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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 |
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Affiliation: | Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F., 04510, México. |
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Abstract: | 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. |
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Keywords: | NMR Potassium Channels Protein Folding Protein Structure Toxins CSα/α fold k-BUTX-Tt2b Scorpion Toxin |
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