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Many peptide toxins are known to specifically and potently block established therapeutic targets, among which the voltage\u2010gated sodium and calcium channels are major contributors. Here, we report on the discovery and characterization of a novel spider toxin isolated from the crude venom of\n                    <jats:italic>Pterinochilus murinus<\/jats:italic>\n                    that shows inhibitory activity at both hNa\n                    <jats:sub>V<\/jats:sub>\n                    1.7 and hCa\n                    <jats:sub>V<\/jats:sub>\n                    3.2 channels, two therapeutic targets implicated in pain pathways. Bioassay\u2010guided HPLC fractionation revealed a 36\u2010amino acid peptide with three disulfide bridges named \u03bc\/\u03c9\u2010theraphotoxin\u2010Pmu1a (Pmu1a). Following isolation and characterization, the toxin was chemically synthesized and its biological activity was further assessed using electrophysiology, revealing Pmu1a to be a toxin that potently blocks both hNa\n                    <jats:sub>V<\/jats:sub>\n                    1.7 and hCa\n                    <jats:sub>V<\/jats:sub>\n                    3. Nuclear magnetic resonance structure determination of Pmu1a shows an inhibitor cystine knot fold that is the characteristic of many spider peptides. Combined, these data show the potential of Pmu1a as a basis for the design of compounds with dual activity at the therapeutically relevant hCa\n                    <jats:sub>V<\/jats:sub>\n                    3.2 and hNa\n                    <jats:sub>V<\/jats:sub>\n                    1.7 voltage\u2010gated channels.\n                  <\/jats:p>","DOI":"10.1111\/febs.16773","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T11:10:13Z","timestamp":1678705813000},"page":"3688-3702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pmu1a, a novel spider toxin with dual inhibitory activity at pain targets hNa\n                    <sub>V<\/sub>\n                    1.7 and hCa\n                    <sub>V<\/sub>\n                    3 voltage\u2010gated channels"],"prefix":"10.1111","volume":"290","author":[{"given":"Julien","family":"Giribaldi","sequence":"first","affiliation":[{"name":"IBMM CNRS, ENSCM, Universit\u00e9 de Montpellier  France"},{"name":"Center for Cancer Research National Cancer Institute, National Institutes of Health  Frederick MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Chemin","sequence":"additional","affiliation":[{"name":"Institute of Functional Genomics CNRS, INSERM, Montpellier University  France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Tuifua","sequence":"additional","affiliation":[{"name":"IBMM CNRS, ENSCM, Universit\u00e9 de Montpellier  France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer R.","family":"Deuis","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Qld 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