Domain 4 of the Anthrax Protective Antigen Maintains Structure and Binding to the Host Receptor CMG2 at Low PH

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2009 Sep 2

PMID 19722284

Citations 12

Authors

Alexander S Williams

Scott Lovell

Asokan Anbanandam

Rahif El-Chami

James G Bann

Affiliations

Soon will be listed here.

Abstract

Domain 4 of the anthrax protective antigen (PA) plays a key role in cellular receptor recognition as well as in pH-dependent pore formation. We present here the 1.95 A crystal structure of domain 4, which adopts a fold that is identical to that observed in the full-length protein. We have also investigated the structural properties of the isolated domain 4 as a function of pH, as well as the pH-dependence on binding to the von Willebrand factor A domain of capillary morphogenesis protein 2 (CMG2). Our results provide evidence that the isolated domain 4 maintains structure and interactions with CMG2 at pH 5, a pH that is known to cause release of the receptor on conversion of the heptameric prepore (PA(63))(7) to a membrane-spanning pore. Our results suggest that receptor release is not driven solely by a pH-induced unfolding of domain 4.

Citing Articles

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Binding of the von Willebrand Factor A Domain of Capillary Morphogenesis Protein 2 to Anthrax Protective Antigen Vaccine Reduces Immunogenicity in Mice.

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Stability of domain 4 of the anthrax toxin protective antigen and the effect of the VWA domain of CMG2 on stability.

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