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PDBsum entry 1vfv
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Transport protein
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PDB id
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1vfv
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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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Kif1a alternately uses two loops to bind microtubules.
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Authors
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R.Nitta,
M.Kikkawa,
Y.Okada,
N.Hirokawa.
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Ref.
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Science, 2004,
305,
678-683.
[DOI no: ]
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PubMed id
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Abstract
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The motor protein kinesin moves along microtubules, driven by adenosine
triphosphate (ATP) hydrolysis. However, it remains unclear how kinesin converts
the chemical energy into mechanical movement. We report crystal structures of
monomeric kinesin KIF1A with three transition-state analogs: adenylyl
imidodiphosphate (AMP-PNP), adenosine diphosphate (ADP)-vanadate, and ADP-AlFx
(aluminofluoride complexes). These structures, together with known structures of
the ADP-bound state and the adenylyl-(beta,gamma-methylene) diphosphate
(AMP-PCP)-bound state, show that kinesin uses two microtubule-binding loops in
an alternating manner to change its interaction with microtubules during the ATP
hydrolysis cycle; loop L11 is extended in the AMP-PNP structure, whereas loop
L12 is extended in the ADP structure. ADP-vanadate displays an intermediate
structure in which a conformational change in two switch regions causes both
loops to be raised from the microtubule, thus actively detaching kinesin.
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Figure 2.
Fig. 2. Crystal structures of KIF1A. (A) The AMP-PNP form of
KIF1A. The switch I, switch II, and neck-linker regions are
highlighted in red. (B) Superposition of AMP-PNP, ADP-AlFx,
ADP-Vi, and ADP structures. The AMP-PNP, ADP-AlFx, ADP-Vi, and
ADP forms are shown in red, blue, green, and yellow,
respectively.
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Figure 3.
Fig. 3. The conformational changes that occur in the two switch
regions and the neck-linker region during ATP hydrolysis. (A to
D) AMP-PCP (A), AMP-PNP (B), ADP-AlFx (C), and ADP-Vi (D) forms
are shown in light brown, red, blue, and green, respectively.
These panels are seen from the upper right in Fig. 2A (indicated
by the black arrow). Nucleotides and the coordinating residues
around them are shown as ball-and-stick models. Missing
C-terminal residues and loops are shown by dashed lines. The
structural details around the nucleotide-binding pocket are also
shown in figs. S2 to S4 (46). (E and F) The conserved salt
bridge between Glu170 and Arg316 (enclosed by a red circle),
shown in ball-and-stick models in the AMP-PNP (E) and ADP-Vi (F)
forms. Loop L8 and the switch II cluster are shown in dark blue
and dark red, respectively. Nucleotides are shown as
space-filling models.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2004,
305,
678-683)
copyright 2004.
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