Biology Reference
In-Depth Information
(FimH or FimF), constituting 50-60% of the total contact surface area (1260
Å
2
). While all components of these two ternary complexes adopt remarkably
similar folds, there are subtle yet significant differences at the FimD NTD-
subunit interface. First, the FimD NTD-FimH interface is 210 Å, larger than the
FimD NTD-FimF interface of 120 Å. Second, the guanidinium moiety of FimD
NTD R7 interacts with FimH via hydrogen bonding with the T200 side chain
and hydrophobic contacts with the T212 side chain, but lacks any contact with
FimF. Third, three hydrogen bonds exist at the FimD NTD-FimH interface -
Y3/Q269, N5/T212, and R7/T200 - while only one hydrogen bond exists at the
FimD NTD-FimF interface - N5/T212 (
Eidam et al., 2008
). Not surprisingly,
FimD NTD has a higher affinity for FimC-FimH than it does for FimC-FimF.
Presumably, the subunits FimG and FimA cannot bind NTD because they
have an incomplete set or total lack of the hydrogen bond interactions with the
N-terminal tail that were detailed above. A similar molecular logic likely holds
true for the selectivity of the NTD domains of other CU ushers, although more
work needs to be done to further bolster this argument.
Given their structural homology, it is not surprising that plug and CTD2 can
recognize nearly all chaperone-subunit complexes. Both the CTD2 and plug
domains of PapC adopt a small beta sandwich fold with a central Greek key motif -
the only difference in fold being an additional β-strand, βG, at the C-terminus
of CTD2 (
Ford et al., 2010
). In addition, many residues are conserved between
the two usher domains. These conserved residues, mainly surface-exposed polar
residues protruding from the βC, βB, βE, and βF side, may hint at a conserved
function for this surface, like binding chaperone-subunit complexes. From the
FimD-FimC-FimH ternary complex, the FimC-FimH complex primarily binds
CTD1 and is seen in proximity to CTD2 (
Phan et al., 2011
). However, FimC-
FimH does not approach CTD2 close enough to form van der Waals contacts
or explain the moderate affinity interaction observed with the isolated domain
(
Volkan et al., 2012
), suggesting the existence of another binding mode between
CTD2 and the chaperone-subunit complexes. Likewise, there is no structural
information regarding the contacts that plug forms with chaperone-subunit
complexes, but given its ability to bind all complexes and chaperone alone, plug
likely forms most of its contacts, if not all, with the chaperone itself. Whether
the βC, βB, βE, and βF side of plug and of CTD2 is involved in binding chap-
erone-subunit complexes remains to be experimentally evaluated. Similarly,
the basis for the terminator's ability to discriminate between plug and CTD2
remains unknown. More work is needed to elucidate the molecular basis of
selectivity by usher domains for chaperone-subunit complexes to better under-
stand the mechanism and subunit ordering of pilus assembly.
Monomer versus dimer
Initial attempts to probe the structure of the usher led to the discovery of a
dimeric state (
Thanassi et al., 1998
). The first of these studies on the PapC usher
Search WWH ::
Custom Search