9UE9

Heptameric pore structure of Vibrio cholerae Cytolysin (VCC) embedded in lipid bilayer

Summary for 9UE9

• Entry DOI: 10.2210/pdb9ue9/pdb
• EMDB information: 31972
• Descriptor: HlyA (2 entities in total)
• Functional Keywords: vibrio cholerae cytolysin (vcc), pore-forming toxin, toxin
• Biological source: Vibrio cholerae
• Total number of polymer chains: 7
• Total formula weight: 452235.69

Authors

Dutta, S.,Chatterjee, A. (deposition date: 2025-04-08, release date: 2025-05-21, Last modification date: 2025-12-03)

Primary citation

Singh, M.,Chatterjee, A.,Nayak, A.,Naskar, P.,Kaur, G.,Mondal, J.,Dutta, S.,Chattopadhyay, K.
Cradle loop regulates beta-barrel pore-formation mechanism of Vibrio cholerae cytolysin.
Structure, 2025

PubMed Abstract: Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin (β-PFT). The membrane insertion of its pore-forming "pre-stem" motif is the most crucial step in the pore-formation mechanism. In the soluble monomeric form, pre-stem remains clamped against the central cytolysin domain by the so-called cradle loop. In the course of oligomeric pore-formation in the target membranes, the cradle loop gets detached from the pre-stem and reorients, thus allowing the pre-stem to extend and insert into the membrane. Here, we show that the specific cradle loop residue(s) play crucial roles in governing the pore-formation mechanism of VCC by establishing decisive interactions with the neighboring structural domains/modules. The alteration of the cradle loop residue, Y194 in particular, compromises the membrane-insertion of the pre-stem, and tends to arrest the membrane-bound toxin in the pre-pore-like oligomeric states. Our study suggests that the native cradle loop architecture, with its intact contacts with the surrounding interaction partners, is essential for VCC pore-formation.

PubMed: 41202807
DOI: 10.1016/j.str.2025.10.013

Experimental method

ELECTRON MICROSCOPY (4 Å)