{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:43:28Z","timestamp":1773657808100,"version":"3.50.1"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:p>Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (Kv) channels that has been proposed to move at the protein\u2013lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit Kv channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin\u2013membrane interaction is not sufficient to inhibit Kv channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin\u2013channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid\u2013channel interactions.<\/jats:p>","DOI":"10.1085\/jgp.200709869","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T00:43:56Z","timestamp":1192495436000},"page":"497-511","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes"],"prefix":"10.1085","volume":"130","author":[{"given":"Mirela","family":"Milescu","sequence":"first","affiliation":[{"name":"1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Vobecky","sequence":"additional","affiliation":[{"name":"1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soung H.","family":"Roh","sequence":"additional","affiliation":[{"name":"2Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung H.","family":"Kim","sequence":"additional","affiliation":[{"name":"2Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoi J.","family":"Jung","sequence":"additional","affiliation":[{"name":"2Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Il","family":"Kim","sequence":"additional","affiliation":[{"name":"2Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenton J.","family":"Swartz","sequence":"additional","affiliation":[{"name":"1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2007,10,15]]},"reference":[{"key":"2023072920522844900_BIB1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tins.2004.03.008","volume":"27","year":"2004","journal-title":"Trends Neurosci."},{"key":"2023072920522844900_BIB2","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0076-6879(99)94013-2","volume":"294","year":"1999","journal-title":"Methods Enzymol."},{"key":"2023072920522844900_BIB3","doi-asserted-by":"crossref","first-page":"11844","DOI":"10.1021\/bi061111z","volume":"45","year":"2006","journal-title":"Biochemistry."},{"key":"2023072920522844900_BIB4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/bi00453a007","volume":"29","year":"1990","journal-title":"Biochemistry."},{"key":"2023072920522844900_BIB5","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/S0006-3495(01)75823-7","volume":"81","year":"2001","journal-title":"Biophys. 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