{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:12:01Z","timestamp":1781143921634,"version":"3.54.1"},"reference-count":0,"publisher":"Acta Naturae Ltd","issue":"1","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Naturae"],"abstract":"<jats:p>Voltage-gated sodium channels (NaV) have a modular architecture and contain five membrane domains. The central pore domain is responsible for ion conduction and contains a selectivity filter, while the four peripheral voltage-sensing domains (VSD-I\/IV) are responsible for activation and rapid inactivation of the channel. Gating modifier toxins from arthropod venoms interact with VSDs, influencing the activation and\/or inactivation of the channel, and may serve as prototypes of new drugs for the treatment of various channelopathies and pain syndromes. The toxin-binding sites located on VSD-I, II and IV of mammalian NaV channels have been previously described. In this work, using the example of the Hm-3 toxin from the crab spider Heriaeus melloteei, we showed the presence of a toxin-binding site on VSD-III of the human skeletal muscle NaV1.4 channel. A developed cell-free protein synthesis system provided milligram quantities of isolated (separated from the channel) VSD-III and its 15N-labeled analogue. The interactions between VSD-III and Hm-3 were studied by NMR spectroscopy in the membrane-like environment of DPC\/LDAO (1 : 1) micelles. Hm-3 has a relatively high affinity to VSD-III (dissociation constant of the complex Kd ~6 M), comparable to the affinity to VSD-I and exceeding the affinity to VSD-II. Within the complex, the positively charged Lys25 and Lys28 residues of the toxin probably interact with the S1S2 extracellular loop of VSD-III. The Hm-3 molecule also contacts the lipid bilayer surrounding the channel.<\/jats:p>","DOI":"10.32607\/actanaturae.11279","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T11:00:20Z","timestamp":1619002820000},"page":"134-139","source":"Crossref","is-referenced-by-count":1,"title":["Voltage-Sensing Domain of the Third Repeat of Human Skeletal Muscle NaV1.4 Channel As a New Target for Spider Gating Modifier Toxins"],"prefix":"10.32607","volume":"13","author":[{"given":"Mikhail Yu.","family":"Myshkin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Paramonov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitrii S.","family":"Kulbatskii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelizaveta A.","family":"Surkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina A.","family":"Berkut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Vassilevski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. N.","family":"Lyukmanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail P.","family":"Kirpichnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-3522","authenticated-orcid":false,"given":"Zakhar O.","family":"Shenkarev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"17808","published-online":{"date-parts":[[2021,3,15]]},"container-title":["Acta Naturae"],"original-title":[],"link":[{"URL":"https:\/\/actanaturae.ru\/2075-8251\/article\/viewFile\/11279\/pdf_1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/actanaturae.ru\/2075-8251\/article\/viewFile\/11279\/pdf_1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T13:48:04Z","timestamp":1636984084000},"score":1,"resource":{"primary":{"URL":"https:\/\/actanaturae.ru\/2075-8251\/article\/view\/11279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,3,15]]}},"URL":"https:\/\/doi.org\/10.32607\/actanaturae.11279","relation":{},"ISSN":["2075-8251"],"issn-type":[{"value":"2075-8251","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3,15]]}}}