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Replacement of negative by positive charges in the presumed membrane-inserted part of diphtheria toxin B fragment. Effect on membrane translocation and on formation of cation channels.
Falnes, P O; Madshus, I H; Sandvig, K; Olsnes, S.
Affiliation
  • Falnes PO; Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway.
J Biol Chem ; 267(17): 12284-90, 1992 Jun 15.
Article in En | MEDLINE | ID: mdl-1376320
Diphtheria toxin B fragment is capable of forming cation-selective channels in the plasma membrane. Such channels may be involved in the translocation of the toxin A fragment to the cytosol. Seven negatively charged amino acids in the B fragment were replaced one by one by lysines, followed by studies of cytotoxicity and channel-forming ability of the different mutants. The mutant D392K showed a strong reduction in binding to cell surface receptors. Of the six mutants that showed wild-type binding affinity, the two mutants D295K and D318K were very inefficient in forming channels. These two mutants had the lowest ability to mediate A fragment translocation. The mutant E362K was able both to induce cation channel formation and to mediate A fragment translocation at a higher pH value than the wild-type B fragment. The results support the notion that formation of cation channels is of importance for the translocation of the A fragment across the plasma membrane, and they indicate that the pH requirement for translocation of the A fragment to the cytosol is partly determined by the B fragment.
Subject(s)
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Collection: 01-internacional Database: MEDLINE Main subject: Diphtheria Toxin / Ion Channels Limits: Animals Language: En Journal: J Biol Chem Year: 1992 Document type: Article Affiliation country: Norway Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Diphtheria Toxin / Ion Channels Limits: Animals Language: En Journal: J Biol Chem Year: 1992 Document type: Article Affiliation country: Norway Country of publication: United States