Council of Scientific & Industrial Research (CSIR)
09/0079(13652)/2022-EMR-I
インド
Science and Engineering Research Board (SERB)
CRG/2022/002674
インド
Science and Engineering Research Board (SERB)
STR/2022/000006
インド
引用
ジャーナル: Structure / 年: 2026 タイトル: Cradle loop regulates β-barrel pore-formation mechanism of Vibrio cholerae cytolysin. 著者: Mahendra Singh / Arnab Chatterjee / Ananya Nayak / Prasenjit Naskar / Gurvinder Kaur / Jagannath Mondal / Somnath Dutta / Kausik Chattopadhyay / 要旨: 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 ...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.