4ATU

Human doublecortin N-DC repeat plus linker, and tubulin (2XRP) docked into an 8A cryo-EM map of doublecortin-stabilised microtubules reconstructed in absence of kinesin

4ATU の概要

• エントリーDOI: 10.2210/pdb4atu/pdb
• 関連するPDBエントリー: 1JFF 1MJD 1SA0 1SA1 1TVK 1Z2B 2BQQ 2WBE 2XRP 4AQV 4AQW
• EMDBエントリー: 2095
• 分子名称: TUBULIN BETA-2B CHAIN, TUBULIN ALPHA-1D CHAIN, NEURONAL MIGRATION PROTEIN DOUBLECORTIN, ... (5 entities in total)
• 機能のキーワード: hydrolase, microtubule-associated protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 446046.74

構造登録者

Liu, J.S.,Schubert, C.R.,Fu, X.,Fourniol, F.J.,Jaiswal, J.K.,Houdusse, A.,Stultz, C.M.,Moores, C.A.,Walsh, C.A. (登録日: 2012-05-09, 公開日: 2012-09-26, 最終更新日: 2024-05-08)

主引用文献

Liu, J.S.,Schubert, C.R.,Fu, X.,Fourniol, F.J.,Jaiswal, J.K.,Houdusse, A.,Stultz, C.M.,Moores, C.A.,Walsh, C.A.
Molecular Basis for Specific Regulation of Neuronal Kinesin- 3 Motors by Doublecortin Family Proteins.
Mol.Cell, 47:707-, 2012

PubMed Abstract: 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.

PubMed: 22857951
DOI: 10.1016/J.MOLCEL.2012.06.025

実験手法

ELECTRON MICROSCOPY (8.3 Å)