@article{d3030bff70ee4f52a7e232ca1384c452,
title = "Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing",
abstract = "Voltage-gated sodium channels are vital membrane proteins essential for electrical signalling; in humans, they are key targets for the development of pharmaceutical drugs. Here we report the crystal structure of an open-channel conformation of NavMs, the bacterial channel pore from the marine bacterium Magnetococcus sp. (strain MC-1). It differs from the recently published crystal structure of a closed form of a related bacterial sodium channel (NavAb) by having its internal cavity accessible to the cytoplasmic surface as a result of a bend/rotation about a central residue in the carboxy-terminal transmembrane segment. This produces an open activation gate of sufficient diameter to allow hydrated sodium ions to pass through. Comparison of the open and closed structures provides new insight into the features of the functional states present in the activation cycles of sodium channels and the mechanism of channel opening and closing.",
author = "McCusker, {Emily C.} and Claire Bagn{\'e}ris and Naylor, {Claire E.} and Cole, {Ambrose R.} and Nazzareno D'Avanzo and Nichols, {Colin G.} and Wallace, {B. A.}",
note = "Funding Information: This work was supported by a project grant from the UK Biotechnology and Biological Science Research Council (BBSRC) to B.A.W., a BBSRC SPORT programme grant to the Membrane Protein Structure Initiative consortium (Professor N. Isaacs, P.I., Univ. of Glasgow) and a grant (HL54171) from the National Institutes of Health (to C.G.N.). We thank Professor David E. Clapham (Harvard Medical School, Boston, MA) for supplying the NavMs gene. We thank the Membrane Protein Laboratory (Diamond Light Source, UK) for their expertise, support and helpful discussions, especially Dr Liz Carpenter and Dr Momi Iwata for assisting in initial crystal set-up, and crystal freezing and synchrotron assistance, and Dr Isabel Moraes and Tian Geng for coordinating experiments and providing valuable tools for screening and testing crystal conditions. We are grateful for the beamline scientists{\textquoteright} help with data collection at the Diamond Light Source, UK (beamlines I24, Dr Gwyndaf Evans; I02, Dr Thomas Sorensen; I03, Dr Katherine McAuley; and I04, Dr Dave Hall), the European Synchrotron Radiation Facility, France (ID23-2, Dr Alexander Popov) and the Swiss Light Source, Switzerland (PXIII beamline, Dr Meitian Wang). We also thank Drs Karin Wallden and Aravindan Ilangovan for strategic collection of the final HEGA-10 crystal data sets.",
year = "2012",
doi = "10.1038/ncomms2077",
language = "English",
volume = "3",
journal = "Nature communications",
issn = "2041-1723",
}