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001-es BibID:	BIBFORM103838
035-os BibID:	(scopus)85132050297 (cikkazonosító)e202213146
Első szerző:	Naseem, Muhammad Umair (biofizikus, molekuláris biológus)
Cím:	Cm28, a scorpion toxin having a unique primary structure, inhibits KV1.2 and KV1.3 with high affinity / Naseem Muhammad Umair, Carcamo-Noriega Edson, Beltrán-Vidal José, Borrego Jesus, Szanto Tibor G., Zamudio Fernando Z., Delgado-Prudencio Gustavo, Possani Lourival D., Panyi Gyorgy
Dátum:	2022
ISSN:	0022-1295 1540-7748
Megjegyzések:	The Cm28 in the venom of Centruroides margaritatus is a short peptide consisting of 27 amino acid residues with a mol wt of 2,820 D. Cm28 has <40% similarity with other known ?-KTx from scorpions and lacks the typical functional dyad (lysine?tyrosine) required to block KV channels. However, its unique sequence contains the three disulfide-bond traits of the ?-KTx scorpion toxin family. We propose that Cm28 is the first example of a new subfamily of ?-KTxs, registered with the systematic number ?-KTx32.1. Cm28 inhibited voltage-gated K+ channels KV1.2 and KV1.3 with Kd values of 0.96 and 1.3 nM, respectively. There was no significant shift in the conductance?voltage (G-V) relationship for any of the channels in the presence of toxin. Toxin binding kinetics showed that the association and dissociation rates are consistent with a bimolecular interaction between the peptide and the channel. Based on these, we conclude that Cm28 is not a gating modifier but rather a pore blocker. In a selectivity assay, Cm28 at 150 nM concentration (>100? Kd value for KV1.3) did not inhibit KV1.5, KV11.1, KCa1.1, and KCa3.1 K+ channels; NaV1.5 and NaV1.4 Na+ channels; or the hHV1 H+ channel but blocked ?27% of the KV1.1 current. In a biological functional assay, Cm28 strongly inhibited the expression of the activation markers interleukin-2 receptor and CD40 ligand in anti-CD3?activated human CD4+ effector memory T lymphocytes. Cm28, due to its unique structure, may serve as a template for the generation of novel peptides targeting KV1.3 in autoimmune diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk KV1.2 KV1.3 scorpion toxin
Megjelenés:	Journal Of General Physiology. - 154 : 8 (2022), p. 1-18. -
További szerzők:	Carcamo-Noriega, Edson Beltrán-Vidal, José Borrego, Jesús Szántó Gábor Tibor (1980-) (vegyész) Zamudio, Fernando Z. Delgado-Prudencio, Gustavo Possani, Lourival Domingos Panyi György (1966-) (biofizikus)
Pályázati támogatás:	K143071 OTKA K142612 OTKA K132906 OTKA CONACYT 303045 Egyéb Tempus Public Foundation Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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