title: Characterization of a novel α-conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors.
abstract: The α3β4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an α-4/6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds. TxID was synthesized using solid phase methods, and the synthetic peptide was functionally tested on nAChRs heterologously expressed in Xenopus laevis oocytes. TxID blocked rat α3β4 nAChRs with a 12.5 nM IC50, which places it among the most potent α3β4 nAChR antagonists. TxID also blocked the closely related α6/α3β4 with a 94 nM IC50 but showed little activity on other nAChR subtypes. NMR analysis showed that two major structural isomers exist in solution, one of which adopts a regular α-CTx fold but with different surface charge distribution to other 4/6 family members. α-CTx TxID is a novel tool with which to probe the structure and function of α3β4 nAChRs.
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drug of Haikou, Hainan University , Haikou Hainan, 570228, China.
authors.forename: Sulan
authors.initials: S
authors.lastname: Luo
authors.forename: Dongting
authors.initials: D
authors.lastname: Zhangsun
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Sean
authors.initials: S
authors.lastname: Christensen
authors.forename: Peta J
authors.initials: PJ
authors.lastname: Harvey
authors.forename: Muharrem
authors.initials: M
authors.lastname: Akcan
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology*; D052078:Conus Snail; D020128:Inhibitory Concentration 50; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014982:Xenopus laevis
chemical_list: D020916:Conotoxins; C059360:Conus textile toxin; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C586740:alpha-conotoxin TxID, Conus textile; C403530:nicotinic receptor alpha3beta4; C104518:nicotinic receptor alpha6