Etter A, Cully D F, Schaeffer J M, Liu K K, Arena J P
Merck Research Laboratories, Department of Cell Biochemistry, Rahway, New Jersey 07065-0900, USA.
J Biol Chem. 1996 Jul 5;271(27):16035-9. doi: 10.1074/jbc.271.27.16035.
Many of the subunits of ligand-gated ion channels respond poorly, if at all, when expressed as homomeric channels in Xenopus oocytes. This lack of a ligand response has been thought to result from poor surface expression, poor assembly, or lack of an agonist binding domain. The Caenorhabditis elegans glutamate-gated chloride channel subunit GluClbeta responds to glutamate as a homomeric channel while the GluClalpha subunit is insensitive. A chimera between GluClalpha and GluClbeta was used to suggest that major determinants for glutamate binding are present on the GluClalpha N terminus. Amino acid substitutions in the presumed pore of GluClalpha conferred direct glutamate gating indicating that GluClalpha is deficient in coupling of ligand binding to channel gating. Heteromeric channels of GluClalpha+beta may differ from the prototypic muscle nicotinic acetylcholine receptor in that they have the potential to bind ligand to all of the subunits forming the channel.
许多配体门控离子通道亚基在非洲爪蟾卵母细胞中以同聚体通道形式表达时，即便有反应也很微弱。这种缺乏配体反应的情况被认为是由于表面表达不佳、组装不良或缺乏激动剂结合域所致。秀丽隐杆线虫的谷氨酸门控氯离子通道亚基GluClβ作为同聚体通道对谷氨酸有反应，而GluClα亚基则无反应。利用GluClα和GluClβ之间的嵌合体表明，谷氨酸结合的主要决定因素存在于GluClα的N端。GluClα假定孔中的氨基酸替换赋予了直接的谷氨酸门控作用，这表明GluClα在配体结合与通道门控的偶联方面存在缺陷。GluClα + β异聚体通道可能与原型肌肉烟碱型乙酰胆碱受体不同，因为它们有可能将配体结合到形成通道的所有亚基上。
