2M3I

Characterization of a Novel Alpha4/6-Conotoxin TxIC from Conus textile that Potently Blocks alpha3beta4 Nicotinic Acetylcholine Receptors

Summary for 2M3I

• Entry DOI: 10.2210/pdb2m3i/pdb
• NMR Information: BMRB: 18964
• Descriptor: Alpha-conotoxin (1 entity in total)
• Functional Keywords: alpha-conotoxin, alpha-helix, disulfide bonds, amidated c-terminus, toxin
• Biological source: Conus lividus
• Cellular location: Secreted (By similarity): H9N3R7
• Total number of polymer chains: 1
• Total formula weight: 1493.82

Authors

Luo, S.,Zhangsun, D.,Zhu, X.,Wu, Y.,Hu, Y.,Christensen, S.,Akcan, M.,Craik, D.J.,McIntosh, J.M. (deposition date: 2013-01-20, release date: 2013-12-04, Last modification date: 2024-10-16)

Primary citation

Luo, S.,Zhangsun, D.,Zhu, X.,Wu, Y.,Hu, Y.,Christensen, S.,Harvey, P.J.,Akcan, M.,Craik, D.J.,McIntosh, J.M.
Characterization of a Novel alpha-Conotoxin TxID from Conus textile That Potently Blocks Rat alpha 3 beta 4 Nicotinic Acetylcholine Receptors.
J.Med.Chem., 56:9655-9663, 2013

PubMed 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.

PubMed: 24200193
DOI: 10.1021/jm401254c

Experimental method

SOLUTION NMR