Disruption of the open conductance in the β-tongue mutants of Cytolysin A

Scientific Reports
Monifa FahieMin Chen

Abstract

Cytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association. Our results suggest that the β-tongue may play an essential structural role in stabilizing the open conformation of the transmembrane domain.

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Citations

Aug 30, 2018·The Journal of Physical Chemistry. B·Fabian DingfelderBenjamin Schuler

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Methods Mentioned

BETA
Gel filtration
circular dichroism
pull down
electron microscopy
PCR
electrophoresis
Fluorescence
pull-down
chip

Software Mentioned

ImageJ
PDBsum
Clampex

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