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

May 22, 2018

Title

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

Author

Monifa A. Fahie, Lucas Liang, Alzira R. Avelino, Bach Pham, Patanachai Limpikirati, Richard W. Vachet, Min Chen

Year

2018

Journal

Scientific Reports

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.

Instrument

J-1500

Keywords

Circular dichroism, Secondary structure, Biochemistry