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Open AccessArticle

Insight into the Structural Dynamics of the Lysenin During Prepore-to-Pore Transition Using Hydrogen–Deuterium Exchange Mass Spectrometry

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 5A Pawinskiego St., 02-106 Warsaw, Poland
2
The Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(8), 462; https://doi.org/10.3390/toxins11080462
Received: 18 July 2019 / Revised: 31 July 2019 / Accepted: 2 August 2019 / Published: 7 August 2019
Lysenin is a pore-forming toxin of the aerolysin family, which is derived from coelomic fluid of the earthworm Eisenia fetida. Upon binding to sphingomyelin (SM)-containing membranes, lysenin undergoes a series of structural changes promoting the conversion of water-soluble monomers into oligomers, leading to its insertion into the membrane and the formation of a lytic β-barrel pore. The soluble monomer and transmembrane pore structures were recently described, but the underlying structural details of oligomerization remain unclear. To investigate the molecular mechanisms controlling the conformational rearrangements accompanying pore formation, we compared the hydrogen–deuterium exchange pattern between lyseninWT and its mutant lyseninV88C/Y131C. This mutation arrests lysenin oligomers in the prepore state at the membrane surface and does not affect the structural dynamics of the water-soluble form of lysenin. In contrast, membrane-bound lyseninV88C/Y131C exhibited increased structural stabilization, especially within the twisted β-sheet of the N-terminal domain. We demonstrated that the structural stabilization of the lysenin prepore started at the site of lysenin’s initial interaction with the lipid membrane and was transmitted to the twisted β-sheet of the N-terminal domain, and that lyseninV88C/Y131C was arrested in this conformation. In lyseninWT, stabilization of these regions drove the conformational changes necessary for pore formation. View Full-Text
Keywords: hydrogen-deuterium exchange; lysenin; pore formation; structure; toxin hydrogen-deuterium exchange; lysenin; pore formation; structure; toxin
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MDPI and ACS Style

Kulma, M.; Dadlez, M.; Kwiatkowska, K. Insight into the Structural Dynamics of the Lysenin During Prepore-to-Pore Transition Using Hydrogen–Deuterium Exchange Mass Spectrometry. Toxins 2019, 11, 462.

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