2LZ5

Solution structure of a Novel Alpha-Conotoxin TxIB

2LZ5 の概要

• エントリーDOI: 10.2210/pdb2lz5/pdb
• NMR情報: BMRB: 18736
• 分子名称: Conotoxin_TxIB (1 entity in total)
• 機能のキーワード: alpha-conotoxin, alpha-helix, disulfide bonds, amidated c-terminus, toxin
• 由来する生物種: Conus textile
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1746.03

構造登録者

Luo, S.,Zhangsun, D.,Wu, Y.,Zhu, X.,Hu, Y.,McIntyre, M.,Christensen, S.,Akcan, M.,Craik, D.,McIntosh, J. (登録日: 2012-09-23, 公開日: 2012-12-05, 最終更新日: 2024-11-20)

主引用文献

Luo, S.,Zhangsun, D.,Wu, Y.,Zhu, X.,Hu, Y.,McIntyre, M.,Christensen, S.,Akcan, M.,Craik, D.J.,McIntosh, J.M.
Characterization of a novel alpha-conotoxin from conus textile that selectively targets alpha6/alpha3beta2beta3 nicotinic acetylcholine receptors.
J.Biol.Chem., 288:894-902, 2013

PubMed Abstract: α6β2 Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons in the CNS are potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine addiction and Parkinson disease. However, recent studies indicate that the α6 subunit can also associate with the β4 subunit to form α6β4 nAChRs that are difficult to pharmacologically distinguish from α6β2, α3β4, and α3β2 subtypes. The current study characterized a novel 16-amino acid α-conotoxin (α-CTx) TxIB from Conus textile whose sequence is GCCSDPPCRNKHPDLC-amide as deduced from gene cloning. The peptide and an analog with an additional C-terminal glycine were chemically synthesized and tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes. α-CTx TxIB blocked α6/α3β2β3 nAChR with an IC(50) of 28 nm. In contrast, the peptide showed little or no block of other tested subtypes at concentrations up to 10 μm. The three-dimensional solution structure of α-CTx TxIB was determined using NMR spectroscopy. α-CTx TxIB represents a uniquely selective ligand for probing the structure and function of α6β2 nAChRs.

PubMed: 23184959
DOI: 10.1074/jbc.M112.427898

実験手法

SOLUTION NMR