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PDBsum entry 4atu
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Contents |
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426 a.a.
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429 a.a.
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107 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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Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins.
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Authors
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J.S.Liu,
C.R.Schubert,
X.Fu,
F.J.Fourniol,
J.K.Jaiswal,
A.Houdusse,
C.M.Stultz,
C.A.Moores,
C.A.Walsh.
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Ref.
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Mol Cell, 2012,
47,
707-721.
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PubMed id
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Abstract
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Doublecortin (Dcx) defines a growing family of microtubule (MT)-associated
proteins (MAPs) involved in neuronal migration and process outgrowth. We show
that Dcx is essential for the function of Kif1a, a kinesin-3 motor protein that
traffics synaptic vesicles. Neurons lacking Dcx and/or its structurally
conserved paralogue, doublecortin-like kinase 1 (Dclk1), show impaired
Kif1a-mediated transport of Vamp2, a cargo of Kif1a, with decreased run length.
Human disease-associated mutations in Dcx's linker sequence (e.g., W146C, K174E)
alter Kif1a/Vamp2 transport by disrupting Dcx/Kif1a interactions without
affecting Dcx MT binding. Dcx specifically enhances binding of the ADP-bound
Kif1a motor domain to MTs. Cryo-electron microscopy and subnanometer-resolution
image reconstruction reveal the kinesin-dependent conformational variability of
MT-bound Dcx and suggest a model for MAP-motor crosstalk on MTs. Alteration of
kinesin run length by MAPs represents a previously undiscovered mode of control
of kinesin transport and provides a mechanism for regulation of MT-based
transport by local signals.
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