@article{6a0bad5dc5884141a3d108f89140fab7,
title = "Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel",
abstract = "Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.",
author = "Cecilia Bouzat and Fernanda Gumilar and Guillermo Spitzmaul and Wang, {Hai Long} and Diego Rayes and Hansen, {Scott B.} and Palmer Taylor and Sine, {Steven M.}",
note = "Funding Information: Acknowledgements We thank J. S. Kim, C. Yu and R. Ho for technical help, J. Rand and C. Bargmann for personal communication and helpful discussions, and all members of the McIntire laboratory for discussions and comments on the manuscript. Some strains were provided by the National Bioresource Project (Japan), the C. elegans Gene Knockout Consortium and the Caenorhabditis Genetics Center. This work was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco, by a grant to S.L.M. from the Department of the Army, by a grant to J.E.R. from NIH and by a development grant to H.K. from the Muscular Dystrophy Association. Funding Information: Acknowledgements This work was supported by grants from the National Institutes of Health, UNS, ANPCyT and F. Antorchas, Argentina.",
year = "2004",
month = aug,
day = "19",
doi = "10.1038/nature02753",
language = "English (US)",
volume = "430",
pages = "896--900",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7002",
}