Long-range stabilization of anthrax protective antigen upon binding to CMG2.

ABSTRACT: Protective antigen (PA) mediates entry of edema factor (EF) and lethal factor (LF) into the cytoplasmic space of the cells through the formation of a membrane-spanning pore. To do this, PA must initially bind to a host cellular receptor. Recent mass spectrometry analysis of PA using histidine hydrogen-deuterium exchange (His-HDX) has shown that binding of the von Willebrand factor A (vWA) domain of the receptor capillary morphogenesis protein-2 (CMG2) lowers the exchange rates of the imidazole C2 hydrogen of several histidines, suggesting that receptor binding decreases the structural flexibility of PA. Here, using His-HDX and fluorescence as a function of denaturant, and protease susceptibility, we show that binding of the vWA domain of CMG2 largely increases the stability of PA and the e

SUBMITTER: Mullangi V 

PROVIDER: S-EPMC4179592 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature