4ATX

Rigor kinesin motor domain with an ordered neck-linker, docked on tubulin dimer, modelled into the 8A cryo-EM map of doublecortin- microtubules decorated with kinesin

Summary for 4ATX

• Entry DOI: 10.2210/pdb4atx/pdb
• Related: 1JFF 1SA0 1SA1 1TVK 1Z2B 2WBE 2XRP 4AQV 4AQW 4ATU
• EMDB information: 2098
• Descriptor: TUBULIN BETA-2B CHAIN, TUBULIN ALPHA-1D CHAIN, KINESIN-1 HEAVY CHAIN, ... (5 entities in total)
• Functional Keywords: hydrolase, microtubule, neck-linker
• Biological source: RATTUS NORVEGICUS (NORWAY RAT); More
• Cellular location: Cytoplasm, cytoskeleton : Q6B856 Q2HJ86 Q2PQA9
• Total number of polymer chains: 3
• Total formula weight: 139247.49

Authors

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. (deposition date: 2012-05-10, release date: 2012-09-26, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (8.2 Å)