Tsetlin V I, Hucho F
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
Membr Cell Biol. 2000;13(2):143-64.
Nicotinic acetylcholine receptor of the electric ray Torpedo is the most comprehensively characterized neurotransmitter receptor. It consists of five subunits (alpha2beta gammadelta) amino acid sequences of which were determined by cDNA cloning and sequencing. The shape and size of the receptor were determined by electron cryomicroscopy. It has two agonist/competitive antagonist binding sites which are located between subunits near the membrane surface. The receptor ion channel is formed by five transmembrane helices (M2) of all five subunits. The position of the binding site for noncompetitive ion channel blockers was found by photoaffinity labelling and site-directed mutagenesis. The intrinsic feature of the receptor structure is the position of the agonist/competitive antagonist binding sites in close vicinity to the ion channel spanning the bilayer membrane. This peculiarity may substantially enhance allosteric transitions transforming the ligand binding into the channel opening and physiological response. Muscle nicotinic acetylcholine receptors from birds and mammals are also pentaoligomers consisting of four different subunits (alpha2beta gammadelta or alpha2beta epsilondelta) with high homology to the Torpedo receptor. Apparently, the pentaoligomeric structure is the main feature of all nicotinic, both muscle and neuronal, receptors. However, the neuronal receptors are formed only by two subunit types (alpha and beta) or are even pentahomomers (alpha7 neuronal receptors). All nicotinic receptors are ligand-gated ion channel, the properties of the channels being essentially determined by amino acid residues forming M2 transmembrane fragments.
电鳐的烟碱型乙酰胆碱受体是特征描述最为全面的神经递质受体。它由五个亚基（α2βγδ）组成，其氨基酸序列通过cDNA克隆和测序得以确定。受体的形状和大小通过电子冷冻显微镜确定。它有两个激动剂/竞争性拮抗剂结合位点，位于靠近膜表面的亚基之间。受体离子通道由所有五个亚基的五个跨膜螺旋（M2）形成。通过光亲和标记和定点诱变确定了非竞争性离子通道阻滞剂的结合位点位置。受体结构的内在特征是激动剂/竞争性拮抗剂结合位点紧邻跨越双层膜的离子通道。这种特性可能会显著增强变构转变，将配体结合转化为通道开放和生理反应。鸟类和哺乳动物的肌肉烟碱型乙酰胆碱受体也是由四个不同亚基（α2βγδ或α2βεδ）组成的五聚体，与电鳐受体具有高度同源性。显然，五聚体结构是所有烟碱型受体（包括肌肉型和神经型）的主要特征。然而，神经型受体仅由两种亚基类型（α和β）形成，甚至是五聚体（α7神经型受体）。所有烟碱型受体都是配体门控离子通道，通道的特性基本上由形成M2跨膜片段的氨基酸残基决定。
