7P1H

Structure of the V. vulnificus ExoY-G-actin-profilin complex

Summary for 7P1H

• Entry DOI: 10.2210/pdb7p1h/pdb
• EMDB information: 13159
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,RTX-toxin, Actin, cytoplasmic 1, Profilin-1, ... (5 entities in total)
• Functional Keywords: bacterial toxin, g-actin, profilin, toxin
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 3
• Total formula weight: 148488.26

Authors

Belyy, A.,Merino, F.,Raunser, S. (deposition date: 2021-07-01, release date: 2021-11-17, Last modification date: 2021-12-01)

Primary citation

Belyy, A.,Merino, F.,Mechold, U.,Raunser, S.
Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens.
Nat Commun, 12:6628-6628, 2021

PubMed 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.

PubMed: 34785651
DOI: 10.1038/s41467-021-26889-2

Experimental method

ELECTRON MICROSCOPY (3.9 Å)