{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:42:38Z","timestamp":1791031358024,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,10,24]],"date-time":"2005-10-24T00:00:00Z","timestamp":1130112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Animal toxins are highly reticulated and structured polypeptides that adopt a limited number of folds. In scorpion species, the most represented fold is the \u03b1\/\u03b2 scaffold in which an helical structure is connected to an antiparallel \u03b2\u2010sheet by two disulfide bridges. The intimate relationship existing between peptide reticulation and folding remains poorly understood. Here, we investigated the role of disulfide bridging on the 3D structure of HsTx1, a scorpion toxin potently active on Kv1.1 and Kv1.3 channels. This toxin folds along the classical \u03b1\/\u03b2 scaffold but belongs to a unique family of short\u2010chain, four disulfide\u2010bridged toxins. Removal of the fourth disulfide bridge of HsTx1 does not affect its helical structure, whereas its two\u2010stranded \u03b2\u2010sheet is altered from a twisted to a nontwisted configuration. This structural change in HsTx1 is accompanied by a marked decrease in Kv1.1 and Kv1.3 current blockage, and by alterations in the toxin to channel molecular contacts. In contrast, a similar removal of the fourth disulfide bridge of Pi1, another scorpion toxin from the same structural family, has no impact on its 3D structure, pharmacology, or channel interaction. These data highlight the importance of disulfide bridging in reaching the correct bioactive conformation of some toxins. Proteins 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.20681","type":"journal-article","created":{"date-parts":[[2005,10,24]],"date-time":"2005-10-24T22:17:16Z","timestamp":1130192236000},"page":"1010-1023","source":"Crossref","is-referenced-by-count":19,"title":["The impact of the fourth disulfide bridge in scorpion toxins of the \u03b1\u2010KTx6 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