Characterization of a Novel α-Conotoxin from Conus textile That Selectively Targets α6/α3β2β3 Nicotinic Acetylcholine Receptors

التفاصيل البيبلوغرافية
العنوان: Characterization of a Novel α-Conotoxin from Conus textile That Selectively Targets α6/α3β2β3 Nicotinic Acetylcholine Receptors
المؤلفون: J. Michael McIntosh, Sulan Luo, Xiaopeng Zhu, Yong Wu, Dongting Zhangsun, David J. Craik, Yuanyan Hu, Muharrem Akcan, Sean Christensen, Melissa McIntyre
المصدر: Journal of Biological Chemistry. 288:894-902
بيانات النشر: Elsevier BV, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Conus textile, genetic structures, Protein subunit, Molecular Conformation, Receptors, Nicotinic, Biology, complex mixtures, Polymerase Chain Reaction, Biochemistry, parasitic diseases, Conus, Animals, Neurotoxin, Conotoxin, Cloning, Molecular, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, Chromatography, High Pressure Liquid, DNA Primers, Acetylcholine receptor, Base Sequence, Peptide chemical synthesis, Conus Snail, Cell Biology, biology.organism_classification, Nicotinic agonist, nervous system, Protein Structure and Folding, sense organs, Conotoxins, Oxidation-Reduction
الوصف: 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.
تدمد: 0021-9258
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c7b9124019ad6166102db5f8a4ecaeeTest
https://doi.org/10.1074/jbc.m112.427898Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....8c7b9124019ad6166102db5f8a4ecaee
قاعدة البيانات: OpenAIRE