Biology Reference
In-Depth Information
MOLECULAR ORGANIZATION
Autotransporters (ATs) are so named based on the hypothesis that all the
functional elements required for secretion are contained in a single protein.
Structurally, AT proteins are characterized by the presence of three distinct
domains: (i) an N-terminal signal sequence; (ii) a secreted passenger/α-domain;
and (iii) a C-terminal domain termed the translocation or β-domain ( Jose et al.,
1995 ). The signal-sequence mediates translocation across the inner membrane
in a Sec-dependent manner. Once in the periplasm the translocation domain
forms a β-barrel composed of 12 β-strands that inserts into the outer mem-
brane ( Henderson et al., 1998; Henderson and Nataro, 2001 ). Finally the
β-barrel mediates translocation of the passenger domain to the surface where
the secreted polypeptide is either cleaved or remains attached to the bacterium
( Henderson et al., 2004 ). While the translocation domain is highly homologous
among AT proteins (conserving the mechanism of transport), the secreted pas-
senger domain demonstrates considerable amino acid sequence variation. ATs
can also vary greatly in length, from as low as 500 aa to above 3000 aa.
Two-partner secretion (TPS) is similar to the AT mechanism, requiring a
passenger domain and a β-barrel translocation domain. However, instead of
being encoded on a single polypeptide, the passenger and translocation domains
are produced as two separate proteins, each containing a Sec-dependent
N-terminal signal sequence to mediate inner-membrane translocation to the
periplasm ( Jacob-Dubuisson et al., 2001 ). These proteins are referred to as
TpsA (passenger) and TpsB (translocation) family members ( Jacob-Dubuisson
et al., 2001 ) and are frequently, but not always, encoded in an operon. Akin to
the AT mechanism, once in the periplasm the translocation β-barrel mediates
secretion of the passenger domain ( Henderson et al., 2000 ). Whilst TpsA pro-
teins can have widely differing functions, they share common features; they are
large (many >3000 aa), they share significant sequence similarity within their
N-terminal 300 aa (a region called the TPS domain) ( Jacob-Dubuisson et al.,
2001, 2004 ) and like the AT passenger domain adopt a β-helical conformation.
The β-barrel of TpsB proteins is different to AT proteins being composed of
16 amphipathic β-strands instead of the usual 12 found in ATs ( Guedin et al.,
2000 ) and containing two polypeptide-transport-associated (POTRA) domains
that descend into the periplasm and are thought to recognize the TpsA pro-
tein via the TPS domain. The POTRA domains are predicted to recruit nascent
β-strands in a process called β-augmentation; in TPS proteins it is thought that
the POTRA motif recognizes the TPS domain of TpsA proteins ( Knowles et al.,
2008; Jacob-Dubuisson et al., 2009; Delattre et al., 2011 ).
The third subgroup, the trimeric autotransporter adhesins (TAA) are pro-
duced as a single polypeptide similar to ATs, however they differ significantly
in the size of the translocation domain. Instead of being comprised of ~300 aa
forming 12 β-strands, a translocation domain of 70-100 aa is sufficient to medi-
ate secretion of the passenger domain ( Roggenkamp et al., 2003; Surana et al.,
Search WWH ::




Custom Search