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PDBsum entry 2onk
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Membrane protein
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PDB id
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2onk
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Contents |
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240 a.a.
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252 a.a.
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311 a.a.
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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 an abc transporter in complex with its binding protein.
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Authors
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K.Hollenstein,
D.C.Frei,
K.P.Locher.
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Ref.
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Nature, 2007,
446,
213-216.
[DOI no: ]
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PubMed id
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Abstract
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ATP-binding cassette (ABC) transporter proteins carry diverse substrates across
cell membranes. Whereas clinically relevant ABC exporters are implicated in
various diseases or cause multidrug resistance of cancer cells, bacterial ABC
importers are essential for the uptake of nutrients, including rare elements
such as molybdenum. A detailed understanding of their mechanisms requires direct
visualization at high resolution and in distinct conformations. Our recent
structure of the multidrug ABC exporter Sav1866 has revealed an outward-facing
conformation of the transmembrane domains coupled to a closed conformation of
the nucleotide-binding domains, reflecting the ATP-bound state. Here we present
the 3.1 A crystal structure of a putative molybdate transporter (ModB2C2) from
Archaeoglobus fulgidus in complex with its binding protein (ModA). Twelve
transmembrane helices of the ModB subunits provide an inward-facing
conformation, with a closed gate near the external membrane boundary. The
ATP-hydrolysing ModC subunits reveal a nucleotide-free, open conformation,
whereas the attached binding protein aligns the substrate-binding cleft with the
entrance to the presumed translocation pathway. Structural comparison of
ModB2C2A with Sav1866 suggests a common alternating access and release
mechanism, with binding of ATP promoting an outward-facing conformation and
dissociation of the hydrolysis products promoting an inward-facing conformation.
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Figure 1.
Figure 1: Overall structure. Front view of the
ModB[2]C[2]A complex in ribbon representation, with the ModB
subunits coloured yellow and blue, the ModC subunits coloured
green and magenta, the binding protein ModA coloured red, and
with bound tungstate in van der Waals representation (yellow
and blue spheres). The grey box depicts the probable location
of the lipid bilayer on the basis of the hydrophobicity of the
protein surface. N, amino terminus; C, carboxy terminus. Note
that there is a vertical two-fold molecular and
non-crystallographic symmetry axis for ModB[2]C[2].
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Figure 2.
Figure 2: ModB architecture and conserved gate regions. a,
View from the extracellular side onto the transmembrane ModB
subunits, with one subunit in yellow ribbon representation, the
other as a blue backbone trace. Helices are numbered as in b,
and conserved motifs forming the closed external gate are
coloured green and red in both subunits. Relevant C  positions
are depicted as black spheres, with their residue numbers
indicated. The conserved Phe 200 is shown in ball-and-stick
representation. b, Topological scheme of the ModB subunit.
Transmembrane helices are numbered consecutively, and short
helices following a transmembrane helix additionally carry
letters. The conserved gate regions are coloured as in a. c,
Alignment of the A. fulgidus ModB sequence with those of other
molybdate and sulphate ABC transporters (abbreviated species
name is followed by an underscore and the ABC transporter name).
Residues with significant conservation are shaded grey. Helices
and conserved motifs are indicated above the sequences.
Conserved gate regions are coloured as in a. TM, transmembrane.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2007,
446,
213-216)
copyright 2007.
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