Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 498

Finally, at the extreme C-terminal of most AT passenger domains there is a
β-strand hairpin structure that forms the autochaperone (AC) domain. This AC
region is essential for folding of β-helical passenger domains, acting as a tem-
plate as the passenger domain is secreted ( Dutta et al., 2003; Oliver et al., 2003 ).
In addition, residues in the AC domain of Hbp are essential for the initiation of
passenger domain translocation ( Soprova et al., 2010 ).
The structure of the passenger domain of TAA proteins has been exten-
sively studied. The crystal structure of the E. coli TAA, EibD has been solved
along with TAAs from other species ( Leo et al., 2011 ). The structure of all
TAAs have a clear organization of an N-terminal head, a connector/neck region,
a stalk which is highly variable in length and a C-terminal anchor domain
( Figure 16.5 ) ( Linke et al., 2006 ). The stalk is a fibrous, highly repetitive struc-
ture rich in coiled coils and extremely variable in length across the TAAs. They
function as spacers to project the head domain away from the bacterial sur-
face; however they also can convey protection against host defenses such as
serum resistance and antibody binding ( Roggenkamp et al., 2003 ). The head
domain of TAA proteins consists of β-sheets forming a coiled left-handed paral-
lel β-roll (LPBR) ( Nummelin et al., 2004 ). Interestingly these are similar to the
β-helix of AT and TPS proteins suggesting that this structure may be important
for either secretion or folding. EibD was the first TAA structure to have both
a head domain and the entire coiled-coil stalk solved. The stalk begins as a
right-handed superhelix, but switches handedness halfway down. Large cavities
were found in the EibD structure that may explain how TAAs bend to bind their
ligands ( Leo et al., 2011 ).
The structure of the passenger domain of the type 5e protein, Intimin from
E. coli, has also been solved ( Luo et al., 2000 ). In contrast to all other passen-
ger domains of T5SS, intimin is composed of 16 β-sheets together with four
α-helices, three of which form Ig-like domains D0, D1, and D2 and the final
forming a lectin-like domain, D3, which binds the translocated intimin receptor
(Tir) ( Figure 16.5 ). Recently the translocation domain of intimin was solved,
revealing a 12-stranded β-barrel reminiscent of the ATs. Indeed, the barrels of
the AT protein EspP and intimin superimpose closely ( Fairman et al., 2012 ).
No structures have been solved in E. coli for members of the TPS pathway,
however the structure has been solved for the prototypical TPS protein, fila-
mentous hemagglutinin (FHA) from Bordetella pertussis. As expected the TpsB
protein forms a 16-stranded β-barrel with two periplasmic POTRA domains
and a large loop harboring a functional important motif ( Jacob-Dubuisson
et al., 2009 ). The TPS domain of the TpsA FHA was also solved and shows a
β-helix, with three extrahelical motifs, a β-hairpin, a four-stranded β-sheet, and
an N-terminal capping, mostly formed by the non-conserved regions of the TPS
domain ( Clantin et al., 2004 ). The structure explains why the TPS domain is
able to initiate folding of the β-helical motifs that form the central domain of the
adhesin, because it is itself a β-helical scaffold. It is likely that the TPS domains
of other TpsA proteins form a similar fold. A β-helical structure has also been