@misc{
 title = {Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin},
 type = {misc},
 year = {2020},
 source = {bioRxiv},
 id = {93dfbda1-07c0-3e23-81eb-4ba42825bd0f},
 created = {2021-02-14T23:59:00.000Z},
 file_attached = {false},
 profile_id = {0633c91d-b6d5-3fcd-9fa3-6021f99f2c58},
 last_modified = {2021-11-18T21:35:19.809Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.  Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels with IC50=11.4 nM. Here we reveal the structure of LqhIII bound to NaV1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na+ permeation, revealing why LqhIII slows inactivation of NaV channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of NaV channels.},
 bibtype = {misc},
 author = {Jiang, D. and Tonggu, L. and Gamal El-Din, T.M. and Banh, R. and Pomès, R. and Zheng, N. and Catterall, W.A.},
 doi = {10.1101/2020.12.28.424592}
}

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It is made available under a CC-BY-NC-ND 4.0 International license. Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels with IC50=11.4 nM. Here we reveal the structure of LqhIII bound to NaV1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na+ permeation, revealing why LqhIII slows inactivation of NaV channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of NaV channels.","bibtype":"misc","author":"Jiang, D. and Tonggu, L. and Gamal El-Din, T.M. and Banh, R. and Pomès, R. and Zheng, N. and Catterall, W.A.","doi":"10.1101/2020.12.28.424592","bibtex":"@misc{\n title = {Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin},\n type = {misc},\n year = {2020},\n source = {bioRxiv},\n id = {93dfbda1-07c0-3e23-81eb-4ba42825bd0f},\n created = {2021-02-14T23:59:00.000Z},\n file_attached = {false},\n profile_id = {0633c91d-b6d5-3fcd-9fa3-6021f99f2c58},\n last_modified = {2021-11-18T21:35:19.809Z},\n read = {false},\n starred = {false},\n authored = {true},\n confirmed = {false},\n hidden = {false},\n private_publication = {true},\n abstract = {The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels with IC50=11.4 nM. Here we reveal the structure of LqhIII bound to NaV1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na+ permeation, revealing why LqhIII slows inactivation of NaV channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of NaV channels.},\n bibtype = {misc},\n author = {Jiang, D. and Tonggu, L. and Gamal El-Din, T.M. and Banh, R. and Pomès, R. and Zheng, N. and Catterall, W.A.},\n doi = {10.1101/2020.12.28.424592}\n}","author_short":["Jiang, D.","Tonggu, L.","Gamal El-Din, T.","Banh, R.","Pomès, R.","Zheng, N.","Catterall, W."],"biburl":"https://bibbase.org/service/mendeley/9435741","bibbaseid":"jiang-tonggu-gamaleldin-banh-poms-zheng-catterall-structuralbasisforvoltagesensortrappingofthecardiacsodiumchannelbyadeathstalkerscorpiontoxin-2020","role":"author","urls":{},"metadata":{"authorlinks":{"pomès, r":"https://pomeslaboratory.github.io/publications/"}},"downloads":7},"bibtype":"misc","creationDate":"2021-02-28T16:31:14.577Z","downloads":7,"keywords":[],"search_terms":["structural","basis","voltage","sensor","trapping","cardiac","sodium","channel","deathstalker","scorpion","toxin","jiang","tonggu","gamal el-din","banh","pomès","zheng","catterall"],"title":"Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin","year":2020,"biburl":"https://bibbase.org/service/mendeley/9435741","dataSources":["Zk8fgif6ZaxWzxDQp","ya2CyA73rpZseyrZ8"]}