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.

journal_name

Arch Biochem Biophys

authors

Chekanov AV,Remacle AG,Golubkov VS,Akatov VS,Sikora S,Savinov AY,Fugere M,Day R,Rozanov DV,Strongin AY

doi

10.1016/j.abb.2005.11.013

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

52-9

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(05)00483-2

journal_volume

446

pub_type

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