Figure 2.
Potential Docking Faces of the Partially Opened State of TolC
(A and B) The second aperture of the channel is less perturbed
in the crystal structures of the partially opened state. A
cross-section through the TolC channel in the closed-state (A)
and open-state C2 crystal form (B) at the level of the second
selectivity filter formed by the ring of D374 residues. While
the outer opening of the channel (as measured by the position of
G365) from the 8.5 A in closed state to about 20 A in the C2
form (Figure 1 Figure 1-C,
Figure S2), the interior second selectivity filter composed of a
ring of D374 deeper in the channel is much less perturbed.
Although the distance between the D374 is extended from about
6.1 A in 1EK9 to up to 8.4 A in the C2 form, it is unlikely to
be sufficient for even small molecules to pass unimpeded, thus
suggesting that a further opening of the channel is required for
transport. This is likely to be activated by the engagement of
the periplasmic partner protein, AcrA. Note the deepening of the
predicted AcrA binding groove in the partially open C2
structure. (C) The intermesh of the loops in the packing of the
TolC open state, showing details of the trimer-trimer contact
interface across a crystallographic symmetry operation in the C2
crystal form. This interaction may mimic the docking of the TolC
into the matching surface of the AcrB (shown in [D]). (D)
Docking model of AcrB and a model of open-state TolC based on
the C2 crystal structure. Colored by chain. The model of the
AcrB-TolC complex was prepared using the asymmetric structures
(2GIF and C2 crystal form of TolC). Although [beta]2 hairpin is
in proximity of H7/H8, it is still capable of interacting with
the H3/H4 residues, in agreement with crosslinking data (Tamura
et al., 2005). Residues indicated by arrows are D153, one of the
residues included in TolC wild-type that maintains the closed
gate; D795 from AcrB, a residue from AcrB [beta]2 hairpin, which
could potentially disrupt D153 interactions; and Y362 (another
gating residue from TolC) and D256 (from [beta]1 hairpin of
AcrB), which in our refined docking model are close to the
interface. Mol Cell. 2008 April 11; 30(1): 114–121. doi:
10.1016/j.molcel.2008.02.015. Copyright [copyright] 2008 ELL &
Excerpta Medica
The above figure is reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2008,
30,
114-121)
copyright 2008.
C,
Figure S2), the interior second selectivity filter composed of a
ring of D374 deeper in the channel is much less perturbed.
Although the distance between the D374 is extended from about
6.1 A in 1EK9 to up to 8.4 A in the C2 form, it is unlikely to
be sufficient for even small molecules to pass unimpeded, thus
suggesting that a further opening of the channel is required for
transport. This is likely to be activated by the engagement of
the periplasmic partner protein, AcrA. Note the deepening of the
predicted AcrA binding groove in the partially open C2
structure. (C) The intermesh of the loops in the packing of the
TolC open state, showing details of the trimer-trimer contact
interface across a crystallographic symmetry operation in the C2
crystal form. This interaction may mimic the docking of the TolC
into the matching surface of the AcrB (shown in [D]). (D)
Docking model of AcrB and a model of open-state TolC based on
the C2 crystal structure. Colored by chain. The model of the
AcrB-TolC complex was prepared using the asymmetric structures
(2GIF and C2 crystal form of TolC). Although [beta]2 hairpin is
in proximity of H7/H8, it is still capable of interacting with
the H3/H4 residues, in agreement with crosslinking data (Tamura
et al., 2005). Residues indicated by arrows are D153, one of the
residues included in TolC wild-type that maintains the closed
gate; D795 from AcrB, a residue from AcrB [beta]2 hairpin, which
could potentially disrupt D153 interactions; and Y362 (another
gating residue from TolC) and D256 (from [beta]1 hairpin of
AcrB), which in our refined docking model are close to the
interface. Mol Cell. 2008 April 11; 30(1): 114–121. doi:
10.1016/j.molcel.2008.02.015. Copyright [copyright] 2008 ELL &
Excerpta Medica