{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T08:04:53Z","timestamp":1793520293038,"version":"4.5.0"},"reference-count":101,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6433","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2019,3,22]]},"abstract":"<jats:title>How activation leads to gating<\/jats:title>\n          <jats:p>\n            Voltage-gated sodium (Na\n            <jats:sub>v<\/jats:sub>\n            ) channels are key players in electrical signaling. Central to their function is fast inactivation, and mutants that impede this cause conditions such as epilepsy and pain syndromes. The channels have four voltage-sensing domains (VSDs), with VSD4 playing an important role in fast inactivation. Clairfeuille\n            <jats:italic>et al.<\/jats:italic>\n            determined the structures of a chimera in which VSD4 of the cockroach channel Na\n            <jats:sub>v<\/jats:sub>\n            PaS is replaced with VSD4 from human Na\n            <jats:sub>v<\/jats:sub>\n            1.7, both in the apo state and bound to a scorpion toxin that impedes fast activation (see the Perspective by Chowdhury and Chanda). The toxin traps VSD4 in a deactivated state. Comparison with the apo structure shows how interactions between VSD4 and the carboxyl-terminal region change as VSD4 activates and suggests how this would lead to fast inactivation.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Science<\/jats:italic>\n            , this issue p.\n            <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" related-article-type=\"in-this-issue\" xlink:href=\"10.1126\/science.aav8573\">eaav8573<\/jats:related-article>\n            ; see also p.\n            <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6433\" page=\"1278\" related-article-type=\"in-this-issue\" vol=\"363\" xlink:href=\"10.1126\/science.aaw8645\">1278<\/jats:related-article>\n          <\/jats:p>","DOI":"10.1126\/science.aav8573","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T00:07:50Z","timestamp":1549584470000},"source":"Crossref","is-referenced-by-count":195,"title":["Structural basis of \u03b1-scorpion toxin action on Na\n            <sub>v<\/sub>\n            channels"],"prefix":"10.1126","volume":"363","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-8928","authenticated-orcid":true,"given":"Thomas","family":"Clairfeuille","sequence":"first","affiliation":[{"name":"Department of Structural Biology, Genentech Inc., South San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-7400","authenticated-orcid":true,"given":"Alexander","family":"Cloake","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Genentech Inc., South San Francisco, CA, USA."},{"name":"Department of Physics, University of Oxford, Oxford OX1 3PU, 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