 |
PDBsum entry 2f1m
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transport protein
|
PDB id
|
|
|
|
2f1m
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Conformational flexibility in the multidrug efflux system protein acra.
|
|
|
Authors
|
|
J.Mikolosko,
K.Bobyk,
H.I.Zgurskaya,
P.Ghosh.
|
|
|
Ref.
|
|
Structure, 2006,
14,
577-587.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Intrinsic resistance to multiple drugs in many gram-negative bacterial pathogens
is conferred by resistance nodulation cell division efflux pumps, which are
composed of three essential components as typified by the extensively
characterized Escherichia coli AcrA-AcrB-TolC system. The inner membrane
drug:proton antiporter AcrB and the outer membrane channel TolC export
chemically diverse compounds out of the bacterial cell, and require the activity
of the third component, the periplasmic protein AcrA. The crystal structures of
AcrB and TolC have previously been determined, and we complete the molecular
picture of the efflux system by presenting the structure of a stable fragment of
AcrA. The AcrA fragment resembles the elongated sickle shape of its homolog
Pseudomonas aeruginosa MexA, being composed of three domains: beta-barrel,
lipoyl, and alpha-helical hairpin. Notably, unsuspected conformational
flexibility in the alpha-helical hairpin domain of AcrA is observed, which has
potential mechanistic significance in coupling between AcrA conformations and
TolC channel opening.
|
|
|
|
|
|
Figure 6.
Figure 6. Comparison of the TolC and AcrA(45-312)-4M
Coiled-Coils
The magnitude of conformational change
predicted for the opening of the TolC channel coincides with the
flexibility observed in the AcrA a-helical hairpin domain. The
inner (yellow) and outer helices (blue) of TolC are shown
superposed based on the internal structural repeat (residues
16-98 and 222-316). Below these are molecules B (red) and C
(green) of AcrA(45-312)-4M, as superposed on the lipoyl domain.
Direct engagement of AcrA and TolC is not modeled.
|
|
|
|
|
|
The above figure is
reprinted
by permission from Cell Press:
Structure
(2006,
14,
577-587)
copyright 2006.
|
|
|
|
|
|
|
