Onset of anthrax toxin pore formation

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Please use this identifier to cite or link to this item: http://hdl.handle.net/1853/41965

Title: Onset of anthrax toxin pore formation
Author: Gao, Mu ; Schulten, Klaus
Abstract: Protective antigen (PA) is the anthrax toxin protein recognized by capillary morphogenesis gene 2 (CMG2), a transmembrane cellular receptor. Upon activation, seven ligand-receptor units self-assemble into a heptameric ring-like complex that becomes endocytozed by the host cell. A critical step in the subsequent intoxication process is the formation and insertion of a pore into the endosome membrane by PA. The pore conversion requires a change in binding between PA and its receptor in the acidified endosome environment. Molecular dynamics simulations totaling ;136 ns on systems of over 92,000 atoms were performed. The simulations revealed how the PA-CMG2 complex, stable at neutral conditions, becomes transformed at low pH upon protonation of His-121 and Glu-122, two conserved amino acids of the receptor. The protonation disrupts a salt bridge important for the binding stability and leads to the detachment of PA domain II, which weakens the stability of the PA-CMG2 complex significantly, and subsequently releases a PA segment needed for pore formation. The simulations also explain the great strength of the PA-CMG2 complex achieves through extraordinary coordination of a divalent cation.
Description: © 2006 by the Biophysical Society
Type: Article
URI: http://hdl.handle.net/1853/41965
ISSN: 0006-3495
Citation: Gao, M, Schulten K. 2006. Onset of anthrax toxin pore formation. Biophysical Journal. 90(9):3267-79.
Date: 2006-05
Contributor: Georgia Institute of Technology. Center for the Study of Systems Biology
Georgia Institute of Technology. School of Biology
University of Illinois at Urbana-Champaign
Beckman Institute for Advanced Science and Technology
Publisher: Georgia Institute of Technology
Biophysical Society
Subject: Anthrax
Protective antigen
Lethal factor
Edema factor
Pore formation

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