The Cys-loop superfamily of ligand-gated ion channels

the impact of receptor structure on function

C. N. Connolly, K. A. Wafford

    Research output: Contribution to journalArticle

    137 Citations (Scopus)

    Abstract

    The Cys-loop receptors constitute an important superfamily of LGICs (ligand-gated ion channels) comprising receptors for acetylcholine, 5-HT3 (5-hydroxytryptamine; S-HT3 receptors), glycine and GABA (gamma-amino-butyric acid; GABA(A) receptors). A vast knowledge of the structure of the Cys-loop superfamily and its impact on channel function have been accrued over the last few years, leading to exciting new proposals on how ion channels open and close in response to agonist binding. Channel opening is initiated by the extracellular association of agonists to discrete binding pockets, leading to dramatic conformational changes, culminating in the opening of a central ion pore. The importance of channel structure is exemplified in the allosteric modulation of channel function by the binding of other molecules to distinct sites on the channel, which exerts an additional level of control on their function. The subsequent conformational changes (gating) lead to channel opening and ion transport. Following channel pore opening, ion selectivity is determined by receptor structure in, and around, the ion pore. As a final level of control, cytoplasmic determinants control the magnitude (conductance) of ion flow into the cell. Thus the Cys-loop receptors are complex molecular motors, with moving parts, which can transduce extracellular signals across the plasma membrane. once the full mechanical motions involved are understood, it may be possible to design sophisticated therapeutic agents to modulate their activity, or at least be able to throw a molecular spanner into the works!

    Original languageEnglish
    Pages (from-to)529-534
    Number of pages6
    JournalBiochemical Society Transactions
    Volume32
    Issue number3
    DOIs
    Publication statusPublished - Jun 2004
    EventBiochemical Society Focused Meeting: Molecular Structure in Ligand-Gated Ion Channel Function - Neuroscience Research Centre, Merck Sharp & Dohme, Harlow, United Kingdom
    Duration: 29 Jan 200429 Jan 2004
    http://www.biochemistry.org/Conferences/AllConferences/tabid/379/View/Conference/Filter/64%2040FC/Page/14/MeetingNo/SA026/Default.aspx

    Cite this

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    abstract = "The Cys-loop receptors constitute an important superfamily of LGICs (ligand-gated ion channels) comprising receptors for acetylcholine, 5-HT3 (5-hydroxytryptamine; S-HT3 receptors), glycine and GABA (gamma-amino-butyric acid; GABA(A) receptors). A vast knowledge of the structure of the Cys-loop superfamily and its impact on channel function have been accrued over the last few years, leading to exciting new proposals on how ion channels open and close in response to agonist binding. Channel opening is initiated by the extracellular association of agonists to discrete binding pockets, leading to dramatic conformational changes, culminating in the opening of a central ion pore. The importance of channel structure is exemplified in the allosteric modulation of channel function by the binding of other molecules to distinct sites on the channel, which exerts an additional level of control on their function. The subsequent conformational changes (gating) lead to channel opening and ion transport. Following channel pore opening, ion selectivity is determined by receptor structure in, and around, the ion pore. As a final level of control, cytoplasmic determinants control the magnitude (conductance) of ion flow into the cell. Thus the Cys-loop receptors are complex molecular motors, with moving parts, which can transduce extracellular signals across the plasma membrane. once the full mechanical motions involved are understood, it may be possible to design sophisticated therapeutic agents to modulate their activity, or at least be able to throw a molecular spanner into the works!",
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    The Cys-loop superfamily of ligand-gated ion channels : the impact of receptor structure on function. / Connolly, C. N. ; Wafford, K. A. .

    In: Biochemical Society Transactions, Vol. 32, No. 3, 06.2004, p. 529-534.

    Research output: Contribution to journalArticle

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    AB - The Cys-loop receptors constitute an important superfamily of LGICs (ligand-gated ion channels) comprising receptors for acetylcholine, 5-HT3 (5-hydroxytryptamine; S-HT3 receptors), glycine and GABA (gamma-amino-butyric acid; GABA(A) receptors). A vast knowledge of the structure of the Cys-loop superfamily and its impact on channel function have been accrued over the last few years, leading to exciting new proposals on how ion channels open and close in response to agonist binding. Channel opening is initiated by the extracellular association of agonists to discrete binding pockets, leading to dramatic conformational changes, culminating in the opening of a central ion pore. The importance of channel structure is exemplified in the allosteric modulation of channel function by the binding of other molecules to distinct sites on the channel, which exerts an additional level of control on their function. The subsequent conformational changes (gating) lead to channel opening and ion transport. Following channel pore opening, ion selectivity is determined by receptor structure in, and around, the ion pore. As a final level of control, cytoplasmic determinants control the magnitude (conductance) of ion flow into the cell. Thus the Cys-loop receptors are complex molecular motors, with moving parts, which can transduce extracellular signals across the plasma membrane. once the full mechanical motions involved are understood, it may be possible to design sophisticated therapeutic agents to modulate their activity, or at least be able to throw a molecular spanner into the works!

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