Both PA63 and PA83 are endocytosed within an anthrax protective antigen mixed heptamer: A putative mechanism to overcome a furin deficiency

Alexei V. Chekanov, Albert G. Remacle, Vladislav S. Golubkov, Vladimir S. Akatov, Sergey Sikora, Alexei Y. Savinov, Martin Fugere, Robert Day, Dmitri V. Rozanov, Alex Y. Strongin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Anthrax toxin consists of protective antigen (PA), and lethal (LF) and edema (EF) factors. A 83 kDa PA monomer (PA83) precursor binds to the cell receptor. Furin-like proprotein convertases (PCs) cleave PA83 to generate cell-bound 63 kDa protein (PA63). PA63 oligomerizes to form a ring-shaped heptamer that binds LF-EF and facilitates their entry into the cells. Several additional PCs, as opposed to furin alone, are capable of processing PA83. Following the incomplete processing of the available pool of PA83, the functional heptamer includes both PA83 and PA63. The available structures of the receptor-PA complex imply that the presence of either one or two molecules of PA83 will not impose structural limitations on the formation of the heptamer and the association of either the (PA83)1(PA63)6 or (PA83)2(PA63)5 heteroheptamer with LF-EF. Our data point to the intriguing mechanism of anthrax that appears to facilitate entry of the toxin into the cells which express limiting amounts of PCs and an incompletely processed PA83 pool.

Original languageEnglish (US)
Pages (from-to)52-59
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume446
Issue number1
DOIs
StatePublished - Feb 1 2006

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Keywords

  • Anthrax
  • Bacillus anthracis
  • Endocytosis
  • Furin
  • Lethal toxin
  • Proprotein convertase
  • Protective antigen

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Chekanov, A. V., Remacle, A. G., Golubkov, V. S., Akatov, V. S., Sikora, S., Savinov, A. Y., Fugere, M., Day, R., Rozanov, D. V., & Strongin, A. Y. (2006). Both PA63 and PA83 are endocytosed within an anthrax protective antigen mixed heptamer: A putative mechanism to overcome a furin deficiency. Archives of Biochemistry and Biophysics, 446(1), 52-59. https://doi.org/10.1016/j.abb.2005.11.013