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

doi:10.1016/j.abb.2005.11.013

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 journal › Article › peer-review

9 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 language	English (US)
Pages (from-to)	52-59
Number of pages	8
Journal	Archives of Biochemistry and Biophysics
Volume	446
Issue number	1
DOIs	https://doi.org/10.1016/j.abb.2005.11.013
State	Published - Feb 1 2006
Externally published	Yes

Keywords

Anthrax
Bacillus anthracis
Endocytosis
Furin
Lethal toxin
Proprotein convertase
Protective antigen

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/j.abb.2005.11.013

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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

Chekanov, AV, Remacle, AG, Golubkov, VS, Akatov, VS, Sikora, S, Savinov, AY, Fugere, M, Day, R, Rozanov, DV & Strongin, AY 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, vol. 446, no. 1, pp. 52-59. https://doi.org/10.1016/j.abb.2005.11.013

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

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.",

keywords = "Anthrax, Bacillus anthracis, Endocytosis, Furin, Lethal toxin, Proprotein convertase, Protective antigen",

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

note = "Funding Information: This work was supported in part by NIH Grants AI056385 and AI61139 (to Strongin) and CIHR Grant MOP-57870 (to R. Day). ",

year = "2006",

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doi = "10.1016/j.abb.2005.11.013",

language = "English (US)",

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T1 - Both PA63 and PA83 are endocytosed within an anthrax protective antigen mixed heptamer

T2 - A putative mechanism to overcome a furin deficiency

AU - Chekanov, Alexei V.

AU - Remacle, Albert G.

AU - Golubkov, Vladislav S.

AU - Akatov, Vladimir S.

AU - Sikora, Sergey

AU - Savinov, Alexei Y.

AU - Fugere, Martin

AU - Day, Robert

AU - Rozanov, Dmitri V.

AU - Strongin, Alex Y.

N1 - Funding Information: This work was supported in part by NIH Grants AI056385 and AI61139 (to Strongin) and CIHR Grant MOP-57870 (to R. Day).

PY - 2006/2/1

Y1 - 2006/2/1

N2 - 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.

AB - 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.

KW - Anthrax

KW - Bacillus anthracis

KW - Endocytosis

KW - Furin

KW - Lethal toxin

KW - Proprotein convertase

KW - Protective antigen

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JO - Archives of Biochemistry and Biophysics

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

Abstract

Keywords

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