Peptide sr11a from Conus spurius is a novel peptide blocker for Kv1 potassium channels.
More than a hundred conotoxins are known today and from them, only seven conopeptides have been identified to target voltage-gated potassium channels (Kv). Conotoxin sr11a belongs to the I(2)-superfamily which is characterized by four disulfide bridges and provokes muscle stiffness when injected intracranially in mice. The aim of this work was to test the biological activity of sr11a on recombinant voltage-gated Kv1 potassium channels expressed in Xenopus laevis oocytes. Peptide sr11a was purified by high-performance liquid chromatography from the venom of the vermivorous Conus spurius. We found that peptide sr11a inhibits the delayed rectifiers Kv1.2 and Kv1.6 but had not effect on the slowly inactivating Kv1.3 channel. The functional dyad composed of a basic Lys and a hydrophobic amino acid residue is a crucial structural element, regarding the binding properties and blocking activities of more than a hundred K(+) channel toxins. Peptide sr11a does not contain Lys residues and then, it lacks the functional dyad. Molecular modeling of peptide sr11a reveals the presence of exposed basic residues of Arg and suggests that Arg17 and Arg29 are important on its biological activity.
Aguilar
Manuel B
MB
Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico.
Pérez-Reyes
Liliana I
LI
López
Zinaeli
Z
de la Cotera
Edgar P Heimer
EP
Falcón
Andrés
A
Ayala
Cicerón
C
Galván
Marcelo
M
Salvador
Carolina
C
Escobar
Laura I
LI
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D052078:Conus Snail / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors*; D014982:Xenopus laevis / Q000378:metabolism
D020916:Conotoxins; D010455:Peptides; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; C552029:Sr11a peptide, Conus spurius