Cytotoxin ClyA from Escherichia coli assembles to a 13-meric pore independent of its redox-state.
ClyA is a pore-forming toxin from virulent Escherichia coli and Salmonella enterica strains. Here, we show that the intrinsic hemolytic activity of ClyA is independent of its redox state, and that the assembly of both reduced and oxidized ClyA to the ring-shaped oligomer is triggered by contact with lipid or detergent. A rate-limiting conformational transition in membrane-bound ClyA monomers precedes their assembly to the functional pore. We obtained a three-dimensional model of the detergent-induced oligomeric complex at 12 A resolution by combining cryo- and negative stain electron microscopy with mass measurements by scanning transmission electron microscopy. The model reveals that 13 ClyA monomers assemble into a cylinder with a hydrophobic cap region, which may be critical for membrane insertion.
Eifler
Nora
N
Maurice E Müller Institute for Microscopy, Biozentrum, University of Basel, Basel, Switzerland.
Vetsch
Michael
M
Gregorini
Marco
M
Ringler
Philippe
P
Chami
Mohamed
M
Philippsen
Ansgar
A
Fritz
Andrea
A
Müller
Shirley A
SA
Glockshuber
Rudi
R
Engel
Andreas
A
Grauschopf
Ulla
U