Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 490

hydrophilic HlyA protein ( Stanley et al., 1998 ). The C-terminal glycine-rich
repeat domain that binds Ca 2+ is required for hemolysis but not for pore for-
mation, and it seems likely that Ca 2+ -induced conformational change may pro-
mote a subsequent insertion of the toxin into cell membranes ( Bakas et al.,
1998; Stanley et al., 1998 ).
In addition to pore formation, at very low, sublytic concentrations, HlyA is
a potent trigger of G-protein-dependent generation of inositol triphosphate and
diacylglycerol in granulocytes and endothelial cells, stimulating the respiratory
burst and the secretion of vesicular constituents ( Bhakdi and Martin, 1991 ). It
has also been shown to stimulate the release of cytokines, including interleukin
1β and tumor necrosis factor (TNF) from a variety of human cells ( Suttorp et al.,
FIGURE 16.2 The structure of trimeric TolC modeled in the closed and open positions. The tri-
meric protein is made of a 40 Å channel domain in the outer membrane and a 100 Å tunnel domain
in the periplasm. Binding of the MFP protein initiates opening of the TolC periplasmic domain by
an iris-like movement enlarging the tunnel diameter from 5 Å to 20 Å. Figure adapted from Protein
Data Bank ( Bavro et al., 2008 ).