Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH approximately 6.0 or below when it is bound to ANTXR1, but only at pH approximately 5.0 or below when it is b...

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Main Authors: Heather M Scobie, John M Marlett, G Jonah A Rainey, D Borden Lacy, R John Collier, John A T Young
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-03-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC1824706?pdf=render
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author Heather M Scobie
John M Marlett
G Jonah A Rainey
D Borden Lacy
R John Collier
John A T Young
author_facet Heather M Scobie
John M Marlett
G Jonah A Rainey
D Borden Lacy
R John Collier
John A T Young
author_sort Heather M Scobie
collection DOAJ
description The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH approximately 6.0 or below when it is bound to ANTXR1, but only at pH approximately 5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation.
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spelling doaj.art-67934455e38744fe9ee74c48ab6cbb642022-12-21T19:16:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-03-0123e32910.1371/journal.pone.0000329Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.Heather M ScobieJohn M MarlettG Jonah A RaineyD Borden LacyR John CollierJohn A T YoungThe anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH approximately 6.0 or below when it is bound to ANTXR1, but only at pH approximately 5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation.http://europepmc.org/articles/PMC1824706?pdf=render
spellingShingle Heather M Scobie
John M Marlett
G Jonah A Rainey
D Borden Lacy
R John Collier
John A T Young
Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
PLoS ONE
title Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
title_full Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
title_fullStr Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
title_full_unstemmed Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
title_short Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
title_sort anthrax toxin receptor 2 determinants that dictate the ph threshold of toxin pore formation
url http://europepmc.org/articles/PMC1824706?pdf=render
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