Skip to Main content Skip to Navigation
New interface
Journal articles

Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens

Abstract : Bacterial human pathogens secrete initially inactive nucleotidyl cyclases that become potent enzymes by binding to actin inside eukaryotic host cells. The underlying molecular mechanism of this activation is, however, unclear. Here, we report structures of ExoY from Pseudomonas aeruginosa and Vibrio vulnificus bound to their corresponding activators F-actin and profilin-G-actin. The structures reveal that in contrast to the apo-state, two flexible regions become ordered and interact strongly with actin. The specific stabilization of these regions results in an allosteric stabilization of the nucleotide binding pocket and thereby to an activation of the enzyme. Differences in the sequence and conformation of the actin-binding regions are responsible for the selective binding to either F- or G-actin. Other nucleotidyl cyclase toxins that bind to calmodulin rather than actin undergo a similar disordered-to-ordered transition during activation, suggesting that the allosteric activation-by-stabilization mechanism of ExoY is conserved in these enzymes, albeit the different activator.
Document type :
Journal articles
Complete list of metadata
Contributor : Undine Mechold Connect in order to contact the contributor
Submitted on : Monday, June 13, 2022 - 12:27:35 PM
Last modification on : Friday, August 5, 2022 - 12:03:01 PM


Distributed under a Creative Commons Attribution 4.0 International License




Alexander Belyy, Felipe Merino, Undine Mechold, Stefan Raunser. Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens. Nature Communications, 2021, 12 (1), pp.6628. ⟨10.1038/s41467-021-26889-2⟩. ⟨pasteur-03694037⟩



Record views


Files downloads