title: New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing.
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.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F., 04510, México.
authors.forename: Alma Leticia
authors.initials: AL
authors.lastname: Saucedo
authors.forename: David
authors.initials: D
authors.lastname: Flores-Solis
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Rodríguez de la Vega
authors.forename: Belén
authors.initials: B
authors.lastname: Ramírez-Cordero
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-López
authors.forename: Patricia
authors.initials: P
authors.lastname: Cano-Sánchez
authors.forename: Roxana
authors.initials: R
authors.lastname: Noriega Navarro
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Valdés
authors.forename: Fredy
authors.initials: F
authors.lastname: Coronas-Valderrama
authors.forename: Adolfo
authors.initials: A
authors.lastname: de Roodt
authors.forename: Luis G
authors.initials: LG
authors.lastname: Brieba
authors.forename: Lourival
authors.initials: L
authors.lastname: Domingos Possani
authors.forename: Federico
authors.initials: F
authors.lastname: del Río-Portilla
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003545:Cysteine / Q000737:chemistry*; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D012605:Scorpions; D020539:Sequence Analysis, Protein; D040681:Structural Homology, Protein; D013499:Surface Properties; D014981:Xenopus
chemical_list: D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms; D003545:Cysteine