Összes szerző

Zamudio Fernando Z.

az alábbi absztraktok szerzői között szerepel:

Muhammad Umair Naseem
Cm39 (α-KTx 4.8): A novel scorpion toxin that inhibits voltage-gated K+ channel Kv1.2 and small- and intermediate-conductance Ca2+-activated K+ channels KCa2.2 and KCa3.1

Aug 30 - szerda

15:30 – 17:00

II. Poszterszekció

P48

Cm39 (α-KTx 4.8): A novel scorpion toxin that inhibits voltage-gated K+ channel Kv1.2 and small- and intermediate-conductance Ca2+-activated K+ channels KCa2.2 and KCa3.1

Muhammad Umair Naseem1, Georgina Gurrola-Briones2, Margarita R. Romero-Imbachi3, Jesus Borrego1, Edson Carcamo-Noriega2, José Beltrán-Vidal3, Fernando Z. Zamudio2, Kashmala Shakeel1, Lourival D. Possani2, Gyorgy Panyi1

1 University of Debrecen, Faculty of Medicine, Department of Biophysics and Cell Biology, Hungary

2 Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Autónoma de México, Mexico

3 Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Cauca, Colombia

A novel peptide toxin, Cm39, was identified in the venom of the Colombian scorpion Centruroides margaritatus. It is composed of 37 amino acid residues with a MW of 3980.2 Da and folded by three disulfide bonds. The Cm39 sequence also contains the Lys-Tyr (KY) functional dyad required to block voltage-gated K+ (Kv) channel. Amino acid sequence comparison with previously known K+ channel inhibitor scorpion toxins (KTx) and phylogenetic analysis revealed that Cm39 is a new member of α-KTx 4 family and registered with systematic number of α-KTx4.8. The full chemical synthesis and proper folding of Cm39 was obtained. The pharmacological properties of the synthetic peptide were determined using patch-clamp electrophysiology. Cm39 inhibits the voltage-gated K+ channel hKv1.2 with high affinity (Kd = 65 nM). The conductance-voltage relationship of Kv1.2 was not altered in the presence of Cm39, the analysis of the toxin binding kinetics was consistent with a bimolecular interaction between the peptide and the channel, and therefore the pore blocking mechanism is proposed for the toxin-channel interaction. Cm39 also inhibits the Ca2+-activated KCa2.2 and KCa3.1 channels, with Kd = 575 nM, and Kd = 59 nM, respectively, however, the peptide does not inhibit hKv1.1, hKv1.3, hKv1.4, hKv1.5, hKv1.6, hKv11.1, mKCa1.1 potassium channels or the hNav1.5 and hNav1.4 sodium channels at 1 µM concentration. Understanding the unusual selectivity profile of Cm39 motivates further experiments to reveal novel interactions with the vestibule of toxin-sensitive channels [1].

References

[1] Naseem MU, Gurrola-Briones G, Romero-Imbachi MR, Borrego J, Carcamo-Noriega E, Beltrán-Vidal J, Zamudio FZ, Shakeel K, Possani LD and Panyi G, (2023) Toxins 15(1), p.41.