Article

Gating of nicotinic ACh receptors: latest insights into ligand binding and function.

Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Department of Health and Human Services, PO Box 12233, Research Triangle Park, NC 27709, USA.
The Journal of Physiology (Impact Factor: 4.54). 11/2009; 588(Pt 4):597-602. DOI: 10.1113/jphysiol.2009.182691
Source: PubMed

ABSTRACT Nicotinic acetylcholine receptors (nAChRs) are in the superfamily of cys-loop receptors, and are widely expressed in the nervous system where they participate in a variety of physiological functions, including regulating excitability and neurotransmitter release, as well as neuromuscular contraction. Members of the cys-loop family of receptors, which also includes the molluscan ACh-binding protein (AChBP), a soluble protein that is analogous to the extracellular ligand-binding domain of the cys-loop receptors, are pentameric assemblies of five subunits, with each subunit arranged around a central 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 AChBP, 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, including a major rearrangement of the C-loop within the ligand binding pocket, and perhaps other regions including the F-loop (the beta8-beta9 linker), the beta1-beta2 linker and the cys-loop. Here I will review the latest findings from my lab aimed at a further understanding of the function of the neuronal nAChR channels (and in particular the role of desensitization), and our search for novel AChBP species that may lead to a further understanding of the function of the cys-loop receptor family.

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