Monitoring anthrax toxin receptor dissociation from the protective antigen by NMR

• DOI: 10.1002/pro.26
• Publication Date: 2009-02-09T23:05:50Z
• Authors: Maheshinie Rajapa...; Jack F. Eichler; Jan Hajduch; David E. Anderson; Kenneth L. Kirk; James G. Bann
• Keywords: Anthrax toxin; Bacillus anthracis; Furin

Abstract The binding of the Bacillus anthracis protective antigen (PA) to host cell receptor is first step toward formation anthrax toxin, a tripartite set proteins that include enzymatic moieties edema factor (EF), and lethal (LF). PA cleaved by furin‐like protease on surface followed donut‐shaped heptameric prepore. prepore undergoes major structural transition at acidic pH results in membrane spanning pore, an event which dictated interactions with necessary for entry EF LF into cell. We provide direct evidence using 1‐dimensional 13 C‐edited 1 H NMR low induces dissociation Von‐Willebrand A domain capillary morphogenesis protein 2 (CMG2) from prepore, but not monomeric full length PA. Receptor also observed carbon‐13 labeled, 2‐fluorohistidine labeled CMG2, consistent studies showing protonation His‐121 CMG2 mechanism release. Dissociation likely caused upon pore state rather than residues or interface.