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Structural Basis of Activation of Cys-Loop Receptors: the Extracellular–Transmembrane Interface as a Coupling Region

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Abstract

Cys-loop receptors mediate rapid transmission throughout the nervous system by converting a chemical signal into an electric one. They are pentameric proteins with an extracellular domain that carries the transmitter binding sites and a transmembrane region that forms the ion pore. Their essential function is to couple the binding of the agonist at the extracellular domain to the opening of the ion pore. How the structural changes elicited by agonist binding are propagated through a distance of 50 Å to the gate is therefore central for the understanding of the receptor function. A step forward toward the identification of the structures involved in gating has been given by the recently elucidated high-resolution structures of Cys-loop receptors and related proteins. The extracellular–transmembrane interface has attracted attention because it is a structural transition zone where β-sheets from the extracellular domain merge with α-helices from the transmembrane domain. Within this zone, several regions form a network that relays structural changes from the binding site toward the pore, and therefore, this interface controls the beginning and duration of a synaptic response. In this review, the most recent findings on residues and pairwise interactions underlying channel gating are discussed, the main focus being on the extracellular–transmembrane interface.

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Acknowledgments

This work was supported by grants from CONICET, Universidad Nacional del Sur, Agencia Nacional de Promoción Científica y Tecnológica, and Fundación Florencio Fiorini to CB.

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Correspondence to Cecilia Bouzat.

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Mariana Bartos and Jeremías Corradi contributed equally to this work.

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Bartos, M., Corradi, J. & Bouzat, C. Structural Basis of Activation of Cys-Loop Receptors: the Extracellular–Transmembrane Interface as a Coupling Region. Mol Neurobiol 40, 236–252 (2009). https://doi.org/10.1007/s12035-009-8084-x

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