Wells Gregg B
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA.
Front Biosci. 2008 May 1;13:5479-510. doi: 10.2741/3094.
The electron diffraction structure of nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata and the X-ray crystallographic structure of acetylcholine binding protein (AChBP) are providing new answers to persistent questions about how nAChRs function as biophysical machines and as participants in cellular and systems physiology. New high-resolution information about nAChR structures might come from advances in crystallography and NMR, from extracellular domain nAChRs as high fidelity models, and from prokaryotic nicotinoid proteins. At the level of biophysics, structures of different nAChRs with different pharmacological profiles and kinetics will help describe how agonists and antagonists bind to orthosteric binding sites, how allosteric modulators affect function by binding outside these sites, how nAChRs control ion flow, and how large cytoplasmic domains affect function. At the level of cellular and systems physiology, structures of nAChRs will help characterize interactions with other cellular components, including lipids and trafficking and signaling proteins, and contribute to understanding the roles of nAChRs in addiction, neurodegeneration, and mental illness. Understanding nAChRs at an atomic level will be important for designing interventions for these pathologies.
来自电鳐的烟碱型乙酰胆碱受体（nAChR）的电子衍射结构以及乙酰胆碱结合蛋白（AChBP）的X射线晶体结构，正在为有关nAChRs如何作为生物物理机器以及作为细胞和系统生理学参与者的长期问题提供新的答案。关于nAChR结构的新的高分辨率信息可能来自晶体学和核磁共振技术的进步、作为高保真模型的细胞外结构域nAChRs以及原核类烟碱蛋白。在生物物理学层面，具有不同药理学特征和动力学的不同nAChRs的结构将有助于描述激动剂和拮抗剂如何与正构结合位点结合、变构调节剂如何通过在这些位点之外结合来影响功能、nAChRs如何控制离子流动以及大的细胞质结构域如何影响功能。在细胞和系统生理学层面，nAChRs的结构将有助于表征与其他细胞成分（包括脂质以及运输和信号蛋白）的相互作用，并有助于理解nAChRs在成瘾、神经退行性变和精神疾病中的作用。在原子水平上理解nAChRs对于设计针对这些病症的干预措施将很重要。
