Order-disorder-order transitions mediate the activation of cholera toxin.

ABSTRACT: Cholera toxin (CT) holotoxin must be activated to intoxicate host cells. This process requires the intracellular dissociation of the enzymatic CTA1 domain from the holotoxin components CTA2 and B5, followed by subsequent interaction with the host factor ADP ribosylation factor 6 (ARF6)-GTP. We report the first NMR-based solution structural data for the CT enzymatic domain (CTA1). We show that this free enzymatic domain partially unfolds at the C-terminus and binds its protein partners at both the beginning and the end of this activation process. Deviations from random coil chemical shifts (Delta delta(coil)) indicate helix formation in the activation loop, which is essential to open the toxin's active site and occurs prior to its association with human protein ARF6. We performed NMR titrat

SUBMITTER: Ampapathi RS 

PROVIDER: S-EPMC2441595 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature