CNF-Sr3 explained

CNF-Sr3, also known as conorfamide-Sr3, is a toxin derived from the venom duct of Conus spurius. CNF-Sr3 is an inhibitor of the Shaker channel, a subtype of the voltage-gated potassium channels.

Etymology and Source

CNF-Sr3 (conorfamide-Sr3) is found in the venom duct of the vermivorous Conus spurius, a marine snail from the Gulf of Mexico.^[1] ^[2]

Chemistry

Structure

CNF-Sr3 consists of 15 amino acid residues and has no cysteine residues. The monoisotopic mass of the protein is 1726.77 Dalton. The sequence of CNF-Sr3 is ATSGPMGWLPVFYRF.

Family

CNF-Sr3 belongs to the conorfamide family, together with CNF-Sr1 5, CNF-Sr2 1 and CNF-Vc1. CNF-Sr1, CNF-Sr2 and CNF-Sr3 are found in the venom duct of Conus spurius. CNF-Vc1 is found in the venom of Conus victoriae.^[3] Conorfamides share sequence similarity with FMRFamide and other FMRFa-related peptides (FaRPs). All conorfamides are disulfide-poor conotoxins.^[4]

Homology

CNF-Sr3 shares 73.3% sequence similarity with CNF-Sr1 and 31.0% sequence similarity with CNF-Sr2. CNF-Sr3 has three additional amino acid residues at the amino-terminus and Leu instead of Val at position 8 compared with CNF-Sr12.

The amino acid sequences of the conorfamides are displayed below:https://www.uniprot.org/uniprot/P85871

Conorfamide-Sr1	Gly-Pro-Met-Gly-Trp-Val-Pro-Val-Phe-Tyr-Arg-Phe
Conorfamide-Sr2	Gly-Pro-Met-Glu-Asp-Pro-Leu-Glu-Ile-Ile-Arg-Ile
Conorfamide-Sr3	Ala-Thr-Ser-Gly-Pro-Met-Gly-Trp-Leu-Pro-Val-Phe-Tyr-Arg-Phe
Conorfamide-Vc1	His-Ser-Gly-Phe-Leu-Leu-Ala-Trp-Ser-Gly-Pro-Arg-Asn-Arg-Phe-Val-Arg-Phe

Target

CNF-Sr3 blocks Shaker K+ channels with a moderate affinity, with a Kd = 2.7 ± 0.35 μM (mean ± SEM). The Shaker channel is a subtype of voltage-gated potassium channels. Inhibition of the Shaker channels by CNF-Sr3 is reversible. This toxin does not block Shab, Shaw, Shal and Eag channels.

External links

Notes and References

Campos-Lira, Elba; Carrillo, Elissa; Aguilar, Manuel B. (2017). Conorfamide-Sr3, a structurally novel specific inhibitor of the Shaker K+ channel. Toxicon. 138: 53-58. doi:10.1016/j.toxicon.2017.07.024.
Maillo, M., M. B. Aguilar, M.B., Lopéz-Vera, E., Craig, A.G., Bulaj, G., Olivera, B.M., Heimer de la Cotera, E.P. (2002). Conorfamide, a Conus venom peptide belonging to the RFamide family of neuropeptides. Toxicon. 40(4): 401-407. doi:10.1016/S0041-0101(01)00176-3.
Robinson, S.D., Safavi-Hemami, H., Raghuraman, S., Imperial, J.S., Papenfusss, A.T., Teichert, R.W., Purcell, A.W., Olivera, B.M., Norton, R.S. (2015). Discovery by protogenomics and characterization of an RF-amide neuropeptide from cone snail venom. J Proteomics. 114: 38-47. doi:10.1016/j.jprot.2014.11.003.
Lebbe, E.K., Tygat J. (2016). In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds. J. Venom Anim. Toxins Incl. Trop. Dis. 22(1): 1-15. doi:10.1186/s40409-016-0083-6.