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PDBsum entry 2hyd
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Transport protein
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PDB id
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2hyd
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References listed in PDB file
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Key reference
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Title
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Structure of a bacterial multidrug abc transporter.
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Authors
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R.J.Dawson,
K.P.Locher.
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Ref.
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Nature, 2006,
443,
180-185.
[DOI no: ]
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PubMed id
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Abstract
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Multidrug transporters of the ABC family facilitate the export of diverse
cytotoxic drugs across cell membranes. This is clinically relevant, as tumour
cells may become resistant to agents used in chemotherapy. To understand the
molecular basis of this process, we have determined the 3.0 A crystal structure
of a bacterial ABC transporter (Sav1866) from Staphylococcus aureus. The
homodimeric protein consists of 12 transmembrane helices in an arrangement that
is consistent with cross-linking studies and electron microscopic imaging of the
human multidrug resistance protein MDR1, but critically different from that
reported for the bacterial lipid flippase MsbA. The observed, outward-facing
conformation reflects the ATP-bound state, with the two nucleotide-binding
domains in close contact and the two transmembrane domains forming a central
cavity--presumably the drug translocation pathway--that is shielded from the
inner leaflet of the lipid bilayer and from the cytoplasm, but exposed to the
outer leaflet and the extracellular space.
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Figure 3.
Figure 3: Transmission interface.
Figure 3 :
Transmission interface. Unfortunately we are unable to
provide accessible alternative text for this. If you
require assistance to access this image, or to obtain a
text description, please contact npg@nature.com-
a, Close-up view of Sav1866 with one subunit in turquoise
ribbon representation, the other in yellow coil representation.
For clarity, only the ICL regions of the transmembrane domains
are shown. Black spheres depict the first and last C  positions
of the 'coupling helices' (see the text). Side chains of
the conserved Glu 473 and Tyr 391 are in ball-and-stick
representation. b, Alignment of the Sav1866 protein sequence
with those of other ABC transporters. Residues with high
conservation are shaded dark grey, those with significant
conservation are shaded light grey, and relevant motifs are
shaded blue and indicated. Residues of the ICLs interacting (4
Å cut-off) with the NBD of the same subunit are indicated
with green shading, and those contacting the opposite NBD with
yellow shading. Residues of the NBD interacting with the TMD are
shown with red shading.
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Figure 5.
Figure 5: ABC exporter schematics.
Figure 5 : ABC
exporter schematics. Unfortunately we are unable to
provide accessible alternative text for this. If you
require assistance to access this image, or to obtain a
text description, please contact npg@nature.com-
a, Earlier cartoons depict two compact transporter halves
(subunits) arranged side-by-side, suggesting separation during
the transport cycle. The grey box indicates the location of the
membrane. b, Schematic of Sav1866 in the observed,
outward-facing conformation. The cartoon emphasizes the domain
swapping and subunit twisting. Arrows indicate the release of
bound drug into the extracellular space.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2006,
443,
180-185)
copyright 2006.
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