Arias H R, Blanton M P
Departments of Pharmacology and Anesthesiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Int J Biochem Cell Biol. 2000 Oct;32(10):1017-28. doi: 10.1016/s1357-2725(00)00051-0.
alpha-Conotoxins (alpha-CgTxs) are a family of Cys-enriched peptides found in several marine snails from the genus Conus. These small peptides behave pharmacologically as competitive antagonists of the nicotinic acetylcholine receptor (AChR). The data indicate that (1) alpha-CgTxs are able to discriminate between muscle- and neuronal-type AChRs and even among distinct AChR subtypes; (2) the binding sites for alpha-CgTxs are located, like other cholinergic ligands, at the interface of alpha and non-alpha subunits (gamma, delta, and epsilon for the muscle-type AChR, and beta for several neuronal-type AChRs); (3) some alpha-CgTxs differentiate the high- from the low-affinity binding site found on either alpha/non-alpha subunit interface; and that (4) specific residues in the cholinergic binding site are energetically coupled with their corresponding pairs in the toxin stabilizing the alpha-CgTx-AChR complex. The alpha-CgTxs have proven to be excellent probes for studying the structure and function of the AChR family.
α-芋螺毒素（α-CgTxs）是一类富含半胱氨酸的肽，存在于芋螺属的几种海洋蜗牛中。这些小肽在药理学上表现为烟碱型乙酰胆碱受体（AChR）的竞争性拮抗剂。数据表明：（1）α-CgTxs能够区分肌肉型和神经元型AChR，甚至能区分不同的AChR亚型；（2）α-CgTxs的结合位点与其他胆碱能配体一样，位于α亚基和非α亚基（肌肉型AChR的γ、δ和ε亚基，以及几种神经元型AChR的β亚基）的界面处；（3）一些α-CgTxs能区分α/非α亚基界面上的高亲和力和低亲和力结合位点；以及（4）胆碱能结合位点中的特定残基与毒素中相应的残基在能量上相互耦合，从而稳定α-CgTx-AChR复合物。事实证明，α-CgTxs是研究AChR家族结构和功能的优秀探针。
