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PDBsum entry 2dfs
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Contractile protein/transport protein
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PDB id
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2dfs
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Contents |
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994 a.a.
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(+ 6 more)
139 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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Three-Dimensional structure of the myosin V inhibited state by cryoelectron tomography.
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Authors
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J.Liu,
D.W.Taylor,
E.B.Krementsova,
K.M.Trybus,
K.A.Taylor.
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Ref.
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Nature, 2006,
442,
208-211.
[DOI no: ]
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PubMed id
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Abstract
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Unconventional myosin V (myoV) is an actin-based molecular motor that has a key
function in organelle and mRNA transport, as well as in membrane trafficking.
MyoV was the first member of the myosin superfamily shown to be processive,
meaning that a single motor protein can 'walk' hand-over-hand along an actin
filament for many steps before detaching. Full-length myoV has a low
actin-activated MgATPase activity at low [Ca2+], whereas expressed constructs
lacking the cargo-binding domain have a high activity regardless of [Ca2+] (refs
5-7). Hydrodynamic data and electron micrographs indicate that the active state
is extended, whereas the inactive state is compact. Here we show the first
three-dimensional structure of the myoV inactive state. Each myoV molecule
consists of two heads that contain an amino-terminal motor domain followed by a
lever arm that binds six calmodulins. The heads are followed by a coiled-coil
dimerization domain (S2) and a carboxy-terminal globular cargo-binding domain.
In the inactive structure, bending of myoV at the head-S2 junction places the
cargo-binding domain near the motor domain's ATP-binding pocket, indicating that
ATPase inhibition might occur through decreased rates of nucleotide exchange.
The actin-binding interfaces are unobstructed, and the lever arm is oriented in
a position typical of strong actin-binding states. This structure indicates that
motor recycling after cargo delivery might occur through transport on actively
treadmilling actin filaments rather than by diffusion.
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Figure 2.
Figure 2: Molecular arrangement within the 'flower' motif. a,
At the top is an opaque surface rendering viewed from the
solvent phase; at the bottom is a translucent surface view with
the myoV atomic model rendered in space filling. The colour
scheme for the bottom molecule is as follows: red and magenta,
motor domains; green, light chains; blue, heavy chain component
of the lever arm; cyan, S2 domain; yellow, cargo-binding domain
density envelope; grey, adjacent molecules. b, c,
Higher-magnification views showing the motor domain fit into the
density envelope. b, View from the solvent phase; c, view from
the monolayer side.
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Figure 4.
Figure 4: Orientation of the myoV-inhibited structure on
F-actin. F-actin strands rendered light blue and grey. Actin
docking is based on ref. 30. a, Panel shows F-actin can bind
only one myoV head at a time. The unbound head extends up
towards the viewer. b, Same view direction as a but with the
second head docked. c, High-magnification gallery of actin-bound
myoV molecules. In some the S2 domain can be seen between the
two heads. Drying in negative stain would flatten the structure
onto a plane, which may account for some of the differences
between the models and the micrographs.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2006,
442,
208-211)
copyright 2006.
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