Tyrosine in the hinge region of the pore-forming motif regulates oligomeric β-barrel pore formation by Vibrio cholerae cytolysin

Mondal, AK and Verma, P and Sengupta, N and Dutta, S and Bhushan Pandit, S and Chattopadhyay, K (2020) Tyrosine in the hinge region of the pore-forming motif regulates oligomeric β-barrel pore formation by Vibrio cholerae cytolysin. In: Molecular Microbiology . (In Press)

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Abstract

β-barrel pore-forming toxins perforate cell membranes by forming oligomeric β-barrel pores. The most crucial step is the membrane-insertion of the pore-forming motifs that create the transmembrane β-barrel scaffold. Molecular mechanism that regulates structural reorganization of these pore-forming motifs during β-barrel pore-formation still remains elusive. Using Vibrio cholerae cytolysin as an archetypical example of the β-barrel pore-forming toxin, we show that a key tyrosine residue (Y321) in the hinge region of the pore-forming motif plays crucial role in this process. Mutation of Y321 abrogates oligomerization of the membrane-bound toxin protomers, and blocks subsequent steps of pore-formation. Our study suggests that the presence of Y321 in the hinge region of the pore-forming motif is crucial for the toxin molecule to sense membrane-binding, and to trigger essential structural rearrangements required for the subsequent oligomerization and pore-formation process. Such a regulatory mechanism of pore-formation by V. cholerae cytolysin has not been documented earlier in the structurally related β-barrel pore-forming toxins. © 2020 John Wiley & Sons Ltd

Item Type:	Journal Article
Publication:	Molecular Microbiology
Publisher:	Blackwell Publishing Ltd
Additional Information:	Copyright for this article belongs to Blackwell Publishing Ltd.
Keywords:	Pore-forming toxin; beta-PFT, Vibrio cholerae cytolysin; protein structure; membrane; oligomerization
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	15 Mar 2021 06:23
Last Modified:	15 Mar 2021 06:23
URI:	http://eprints.iisc.ac.in/id/eprint/67229

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