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PDBsum entry 3h4s
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Motor protein/calcium binding protein
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PDB id
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3h4s
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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 the complex of a mitotic kinesin with its calcium binding regulator.
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Authors
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M.V.Vinogradova,
G.G.Malanina,
A.S.Reddy,
R.J.Fletterick.
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Ref.
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Proc Natl Acad Sci U S A, 2009,
106,
8175-8179.
[DOI no: ]
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PubMed id
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Abstract
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Much of the transport, tension, and movement in mitosis depends on kinesins, the
ATP-powered microtubule-based motors. We report the crystal structure of a
kinesin complex, the mitotic kinesin KCBP bound to its principal regulator KIC.
Shown to be a Ca(2+) sensor, KIC works as an allosteric trap. Extensive
intermolecular interactions with KIC stabilize kinesin in its ADP-bound
conformation. A critical component of the kinesin motile mechanism, called the
neck mimic, switches its association from kinesin to KIC, stalling the motor.
KIC denies access of the motor to its track by steric interference. Two major
features of this regulation, allosteric trapping and steric blocking, are likely
to be general for all kinesins.
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Figure 1.
Three-dimensional organization of complex between kinesin
motor KCBP and regulatory Ca^2+-binding protein KIC. (A)
Schematic illustration of complex components. The fragments of
KCBP and KIC visualized in the crystal structure are traced in
orange for KCBP and in green for KIC. The domain structure of
KCBP is depicted. (B) Crystal structure of the complex of
kinesin KCBP and KIC solved at a resolution of 2.4 Å. The
motor (light orange) and KIC (green) are shown schematically.
ADP (light blue) and Ca^2+ ion (black) are space-filling models.
The regulatory domain of KCBP is highlighted in orange. (C and
D) Two views of the structure of KIC in the complex. In C, KIC
is shown in orientation allowing visualization of the part
corresponding to the central helix of the Ca^2+ sensors
(calmodulin, troponin C). The C-terminal part of the
“central” helix in KIC is less ordered than its N-terminal
half. For alignment of KIC with troponin C and calmodulin,
please see Table S2. In D, the EF-hands helices are indicated
(A, B, C, D) as the similar elements in the structures of Ca^2+
sensors. The β-sheet stabilizing the EF-hand pair is shown in
cyan.
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Figure 4.
The conformational change in KCBP accompanying ATP
hydrolysis. (A) The structure of KCBP-KIC complex is superposed
with the structure of KCBP alone (PDB ID code 3cob, chain A).
Only the switch II helix α4 and the regulatory elements (in
pink) of the solo KCBP structure are shown. The analogous
elements of KCBP in the structure of the complex are highlighted
in orange. For our previous crystallographic studies of KCBP
(PDB ID codes 1sdm, 3cob, 3cnz), we used KCBP from potato (amino
acids 884-1252) that is 80% identical to Arabidopsis KCBP. (B)
The hydrophobic pocket (marked in yellow) on the kinesin surface
(gray) is occupied by Ile-1210 in the ATP-like conformation. (C)
The shifted hydrophobic pocket (marked in yellow) on the kinesin
surface (gray) is occupied by Ile-890 of the β1 strand as found
in the ADP state. Ile-1210 is expelled from the hydrophobic
pocket on the kinesin surface and interacts with KIC (Fig. 3).
Hydrophobic residues are conserved at positions 890 and 1210 in
all kinesins. Helices α4 and α6 and the β1 strand of KCBP
(indicated) are shown schematically and are visible through the
translucent surface. The neck mimic is shown as a coil and is
colored according to the conformational state.
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