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DC Field | Value | Language |
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dc.contributor.author | Mondal, Anish Kumar | - |
dc.contributor.author | Singh, Mahendra | - |
dc.contributor.author | Lata, Kusum | - |
dc.contributor.author | Lahiri, Indrajit | - |
dc.contributor.author | Chattopadhyay, Kausik | - |
dc.date.accessioned | 2023-08-17T17:06:29Z | - |
dc.date.available | 2023-08-17T17:06:29Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Journal of Biological Chemistry, 298(10), 102441. | en_US |
dc.identifier.uri | https://doi.org/10.1016/j.jbc.2022.102441 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/4802 | - |
dc.description | Only IISERM authors are available in the record | en_US |
dc.description.abstract | Vibrio cholerae cytolysin (VCC) is a potent membrane-damaging β-barrel pore-forming toxin. Upon binding to the target membranes, VCC monomers first assemble into oligomeric prepore intermediates and subsequently transform into transmembrane β-barrel pores. VCC harbors a designated pore-forming motif, which, during oligomeric pore formation, inserts into the membrane and generates a transmembrane β-barrel scaffold. It remains an enigma how the molecular architecture of the pore-forming motif regulates the VCC pore-formation mechanism. Here, we show that a specific pore-forming motif residue, E289, plays crucial regulatory roles in the pore-formation mechanism of VCC. We find that the mutation of E289A drastically compromises pore-forming activity, without affecting the structural integrity and membrane-binding potential of the toxin monomers. Although our single-particle cryo-EM analysis reveals WT-like oligomeric β-barrel pore formation by E289A-VCC in the membrane, we demonstrate that the mutant shows severely delayed kinetics in terms of pore-forming ability that can be rescued with elevated temperature conditions. We find that the pore-formation efficacy of E289A-VCC appears to be more profoundly dependent on temperature than that of the WT toxin. Our results suggest that the E289A mutation traps membrane-bound toxin molecules in the prepore-like intermediate state that is hindered from converting into the functional β-barrel pores by a large energy barrier, thus highlighting the importance of this residue for the pore-formation mechanism of VCC. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier | en_US |
dc.subject | Glu289 residue in the pore-forming | en_US |
dc.subject | motif of Vibrio cholerae cytolysin | en_US |
dc.subject | β-barrel pore formation | en_US |
dc.subject | protein structure | en_US |
dc.title | Glu289 residue in the pore-forming motif of Vibrio cholerae cytolysin is important for efficient β-barrel pore formation | en_US |
dc.type | Article | en_US |
Appears in Collections: | Research Articles |
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