Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 493

2004 ). This shorter translocation domain has been shown to form four β-strands
which only become a functional 12-stranded β-barrel by forming a homotrimer
in the outer membrane ( Cotter et al., 2005; Linke et al., 2006 ). Trimerization
of the passenger domain is vital for stability and functionality of the protein
( Cotter et al., 2006 ). As the name suggests all TAA proteins identified to date
have a role in adhesion.
Recently, a patatin-like protein named PlpD was identified in an environ-
mental Pseudomonas strain and described to belong to a fourth sub-group of
T5SS ( Salacha et al., 2010 ). Like the classical ATs, the protein is produced as
a single polypeptide with an N-terminal signal sequence, a passenger domain
and a β-barrel translocation unit, however the β-barrel domain in type 5d is
composed of 16 β-strands and more closely related to the TpsB proteins of
two-partner secretion. There is also a POTRA motif between the passenger and
translocation domains, suggesting a gene fusion event combining the two com-
ponents of a TPS system. No members of the type 5d have been identified in
E. coli and these proteins will not be considered further here.
Finally, Intimin of E. coli (see Chapters 4 and 5) and Invasin of Yersinia,
have long been studied for their role in adhesion but due to their vastly differ-
ent genetic organization they have only recently been identified as belonging
to T5SS. The proteins possess an N-terminal signal sequence, but in contrast to
classical ATs, the order of the passenger and translocation domains are reversed
( Tsai et al., 2010 ). In addition to this reversal, between the translocation β-barrel
and signal peptide is an α-helical region and a LysM domain thought to bind to
peptidoglycan ( Fairman et al., 2012 ). The β-barrel, similar to classical ATs, is
composed of 12 β-strands ( Fairman et al., 2012 ). The inverted domain structure
results in the C-terminus, not the N-terminus being secreted to the cell surface
where it extends from the outer membrane to contact the host cell.
SECRETION
It was initially hypothesized that T5SS proteins were unique in that all elements
required for secretion were found in either one or two proteins. However, recent
studies reveal that the reality is more complicated, with periplasmic chaperones
and machinery in the inner and outer membranes also required for secretion.
The majority of work on T5SS secretion has been focused on classical ATs, so
that little is yet known about the requirements of types 5b-e secreted proteins.
However as the subgroups have many similarities in structure and domain orga-
nization it would be unsurprising if they shared many of the requirements of
classical ATs.
All five subgroups of T5SS once translated are targeted to the Sec machin-
ery, which catalyzes their energy-driven transport to the periplasm. Most T5SS
proteins are synthesized with characteristic Sec-dependent signal peptides,
typically 20-30 aa in length. These signal peptides typically consist of a pos-
itively charged N-domain, followed by a hydrophobic H domain and finally