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PDBsum entry 1f9w
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Contractile protein
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PDB id
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1f9w
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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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A structural pathway for activation of the kinesin motor atpase.
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Authors
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M.Yun,
X.Zhang,
C.G.Park,
H.W.Park,
S.A.Endow.
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Ref.
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EMBO J, 2001,
20,
2611-2618.
[DOI no: ]
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PubMed id
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Abstract
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Molecular motors move along actin or microtubules by rapidly hydrolyzing ATP and
undergoing changes in filament-binding affinity with steps of the nucleotide
hydrolysis cycle. It is generally accepted that motor binding to its filament
greatly increases the rate of ATP hydrolysis, but the structural changes in the
motor associated with ATPase activation are not known. To identify the
conformational changes underlying motor movement on its filament, we solved the
crystal structures of three kinesin mutants that decouple nucleotide and
microtubule binding by the motor, and block microtubule-activated, but not
basal, ATPase activity. Conformational changes in the structures include a
disordered loop and helices in the switch I region and a visible switch II loop,
which is disordered in wild-type structures. Switch I moved closer to the bound
nucleotide in two mutant structures, perturbing water-mediated interactions with
the Mg2+. This could weaken Mg2+ binding and accelerate ADP release to activate
the motor ATPASE: The structural changes we observe define a signaling pathway
within the motor for ATPase activation that is likely to be essential for motor
movement on microtubules.
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Figure 1.
Figure 1 Wild-type Kar3 and mutated residues. (A) The conserved
switch I (SwI, green) and switch II (SwII, cyan) residues are
indicated in Kar3+N11 together with helices  3
and 4
(gray). The switch II loop between R632 and the end of helix
4
(dotted line) is disordered and is not present in the model.
Residues mutated in the Kar3 N650K uncoupling mutant (gray),
Kar3 SwII R632A mutant (gray) and Kar3 salt-bridge mutants
(R598A, green; E631A, cyan) are shown space-filled and enlarged
in (B). (B) N650 of the Kar3 N650K uncoupling mutant interacts
with R632 of SwII in wild-type Kar3. The salt bridge forms
between R598 of SwI and E631 of SwII in wild-type Kar3. ADP
(black) and Mg2+ (red) are shown as ball-and-stick models.
Figure produced using RIBBONS (Carson, 1997).
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Figure 5.
Figure 5 Coordination of the Mg2+ ion in wild-type Kar3. The
bound Mg2+ of wild-type Kar3 has a tetragonal bipyramidal or
octahedral coordination due to the P[  ]oxygen,
the hydroxyl group of T481 and four water molecules that also
interact with D626 of switch II (cyan), R585 and T587 of loop
L9, and N593 of helix 3a.
R585 is hydrogen bonded by a water molecule to the D626 side
chain that interacts with the Mg2+.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
2611-2618)
copyright 2001.
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