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PDBsum entry 1i5s
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Transport protein
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PDB id
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1i5s
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Switch-Based mechanism of kinesin motors.
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Authors
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M.Kikkawa,
E.P.Sablin,
Y.Okada,
H.Yajima,
R.J.Fletterick,
N.Hirokawa.
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Ref.
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Nature, 2001,
411,
439-445.
[DOI no: ]
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PubMed id
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Abstract
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Kinesin motors are specialized enzymes that use hydrolysis of ATP to generate
force and movement along their cellular tracks, the microtubules. Although
numerous biochemical and biophysical studies have accumulated much data that
link microtubule-assisted ATP hydrolysis to kinesin motion, the structural view
of kinesin movement remains unclear. This study of the monomeric kinesin motor
KIF1A combines X-ray crystallography and cryo-electron microscopy, and allows
analysis of force-generating conformational changes at atomic resolution. The
motor is revealed in its two functionally critical states-complexed with ADP and
with a non-hydrolysable analogue of ATP. The conformational change observed
between the ADP-bound and the ATP-like structures of the KIF1A catalytic core is
modular, extends to all kinesins and is similar to the conformational change
used by myosin motors and G proteins. Docking of the ADP-bound and ATP-like
crystallographic models of KIF1A into the corresponding cryo-electron microscopy
maps suggests a rationale for the plus-end directional bias associated with the
kinesin catalytic core.
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Figure 2.
Figure 2: Nucleotide-dependent movements of the mechanical
elements of kinesin motors. a, Reorientation of the neck
linker between the ADP (yellow) and ATP-like (red) states of
KIF1A. b, Superposition of the switch II clusters of the
plus-end-directed kinesins. Conformation of the switch II
cluster (ADP or ATP-like, yellow and red, respectively) controls
position of the kinesin neck linker in all structures. Helix
 6
is shown in blue. c, Hypothetical model for the
nucleotide-dependent dynamics at the core/neck interface of the
minus-end-directed motor ncd^9. The colours are the same as in a
and b. The switch II cluster and the neck in ATP state are
dashed. Conserved residues essential for stabilization of the
neck/core interface in the ADP state of the ncd^9 are labelled.
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Figure 3.
Figure 3: Cryo-EM maps of the microtubules decorated by the
KIF1A. a, A 22 Å resolution map of the KIF1A -AMPPNP
-microtubule complex15. The motor core (yellow) and its long
axis (red line) are shown. The microtubules are shown with their
plus end up in this and following figures. b, Docking of the
ATP-like KIF1A crystal structure into 15 Å resolution cryo-EM
map of the microtubule (grey) complexed with the KIF1A (yellow)
in the presence of AMPPNP15. The C-terminal region of tubulin
(E-hook) is shown in yellow. c, A 22 Å resolution map of the
KIF1A -ADP -microtubule complex. The long axis of the motor is
indicated by a red line. For comparison, its orientation in the
ATP-like state is indicated by the orange grid and pink line. d,
Docking of the ADP-bound KIF1A crystal structure into
electron-microscopy-derived 22 Å resolution map. The colours are
the same as in b.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
411,
439-445)
copyright 2001.
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