Gay Elaine A, Yakel Jerrel L
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
J Physiol. 2007 Nov 1;584(Pt 3):727-33. doi: 10.1113/jphysiol.2007.142554. Epub 2007 Sep 6.
Nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys-loop ligand-gated ion channels, and are pentameric assemblies of five subunits, with each subunit arranged around the central ion-conducting pore. The binding of ACh to the extracellular interface between two subunits induces channel opening. With the recent 4 A resolution of the Torpedo nAChR, and the crystal structure of the related molluscan ACh binding protein, much has been learned about the structure of the ligand binding domain and the channel pore, as well as major structural rearrangements that may confer channel opening. For example, the putative pathway coupling agonist binding to channel gating may include a major rearrangement of the C-loop within the ligand binding pocket, and the disruption of a salt bridge between an arginine residue at the end of the beta10 strand and a glutamate residue in the beta1-beta2 linker. Here we will review and discuss the latest structural findings aiming to further refine the transduction pathway linking binding to gating for the nAChR channels, and discuss similarities and differences among the different members of this Cys-loop superfamily of receptors.
烟碱型乙酰胆碱受体（nAChRs）属于半胱氨酸环配体门控离子通道超家族，是由五个亚基组成的五聚体，每个亚基围绕着中央离子传导孔排列。乙酰胆碱（ACh）与两个亚基之间的细胞外界面结合会诱导通道开放。随着近期电鳐nAChR达到4埃的分辨率以及相关软体动物ACh结合蛋白的晶体结构的确定，人们对配体结合域和通道孔的结构，以及可能导致通道开放的主要结构重排有了很多了解。例如，推测的将激动剂结合与通道门控相偶联的途径可能包括配体结合口袋内C环的重大重排，以及β10链末端的精氨酸残基与β1-β2连接子中的谷氨酸残基之间盐桥的破坏。在此，我们将回顾和讨论最新的结构发现，旨在进一步完善nAChR通道将结合与门控联系起来的转导途径，并讨论该半胱氨酸环受体超家族不同成员之间的异同。
