Structure and Mode of Action of a Mosquitocidal Holotoxin

Nora Treiber, Dirk J. Reinert, Irina Carpusca, Klaus Aktories, Georg E. Schulz*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

Abstract

The crystal structure of the full mosquitocidal toxin from Bacillus sphaericus (MTXholo) has been determined at 2.5 Å resolution by the molecular replacement method. The resulting structure revealed essentially the complete chain consisting of four ricin B-type domains curling around the catalytic domain in a hedgehog-like assembly. As the structure was virtually identical in three different crystal packings, it is probably not affected by packing contacts. The structure of MTXholo explains earlier autoinhibition data. An analysis of published complexes comprising ricin B-type lectin domains and sugar molecules shows that the general construction principle applies to all four lectin domains of MTXholo, indicating 12 putative sugar-binding sites. These sites are sequence-related to those of the cytotoxin pierisin from cabbage butterfly, which are known to bind glycolipids. It seems therefore likely that MTXholo also binds glycolipids. The seven contact interfaces between the five domains are predominantly polar and not stronger than common crystal contacts so that in an appropriate environment, the multidomain structure would likely uncurl into a string of single domains. The structure of the isolated catalytic domain plus an extended linker was established earlier in three crystal packings, two of which showed a peculiar association around a 7-fold axis. The catalytic domain of the reported MTXholo closely resembles all three published structures, except one with an appreciable deviation of the 40 N-terminal residues. A comparison of all structures suggests a possible scenario for the translocation of the toxin into the cytosol.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalJournal of Molecular Biology
Volume381
Issue number1
DOIs
Publication statusPublished - 1 Aug 2008
Externally publishedYes

Keywords

  • X-ray diffraction
  • disassembly of multidomain protein
  • pierisin
  • ricin B-type lectin domains
  • translocation model

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