A gating mechanism proposed from a simulation of a human α7 nicotinic acetylcholine receptor

Richard J. Law, Richard H. Henchman, J. Andrew McCammon

    Research output: Contribution to journalArticlepeer-review


    The nicotinic acetylcholine receptor is a well characterized ligand-gated ion channel, yet a proper description of the mechanisms involved in gating, opening, closing, ligand binding, and desensitization does not exist. Until recently, atomic-resolution structural information on the protein was limited, but with the production of the x-ray crystal structure of the Lymnea stagnalis acetylcholine binding protein and the EM image of the transmembrane domain of the torpedo electric ray nicotinic channel, we were provided with a window to examine the mechanism by which this channel operates. A 15-ns all-atom simulation of a homology model of the homomeric human α7 form of the receptor was conducted in a solvated palmitoyl-2-oleoyl-sn-glycerol- phosphatidylcholine bilayer and examined in detail. The receptor was unliganded. The structure undergoes a twist-to-close motion that correlates movements of the C loop in the ligand binding domain, via the β10-strand that connects the two, with the 10° rotation and inward movement of two nonadjacent subunits. The Cys loop appears to act as a stator around which the α-helical transmembrane domain can pivot and rotate relative to the rigid β-sheet binding domain. The M2-M3 loop may have a role in controlling the extent or kinetics of these relative movements. All of this motion, along with essential dynamics analysis, is suggestive of the direction of larger motions involved in gating of the channel. © 2005 by The National Academy of Sciences of the USA.
    Original languageEnglish
    Pages (from-to)6813-6818
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number19
    Publication statusPublished - 10 May 2005


    Dive into the research topics of 'A gating mechanism proposed from a simulation of a human α7 nicotinic acetylcholine receptor'. Together they form a unique fingerprint.

    Cite this