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J Cell Biol. 2018 Dec 3;217(12):4155-4163. doi: 10.1083/jcb.201711182. Epub 2018 Oct 1.

Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs.

Author information

1
RIKEN Center for Life Science Technologies, Yokohama, Japan.
2
RIKEN SPring-8 Center, Hyogo, Japan.
3
Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
4
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
5
Division of Applied Science and Engineering, Course of Biosystem, Graduate School of Muroran Institute of Technology, Muroran, Japan.
6
RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan.
7
RIKEN Center for Life Science Technologies, Yokohama, Japan ryonitta@med.kobe-u.ac.jp.

Abstract

The Tau family microtubule-associated proteins (MAPs) promote microtubule stabilization and regulate microtubule-based motility. They share the C-terminal microtubule-binding domain, which includes three to five tubulin-binding repeats. Different numbers of repeats formed by alternative splicing have distinct effects on the activities of these proteins, and the distribution of these variants regulates fundamental physiological phenomena in cells. In this study, using cryo-EM, we visualized the MAP4 microtubule complex with the molecular motor kinesin-1. MAP4 bound to the C-terminal domains of tubulins along the protofilaments stabilizes the longitudinal contacts of the microtubule. The strongest bond of MAP4 was found around the intertubulin-dimer interface such that MAP4 coexists on the microtubule with kinesin-1 bound to the intratubulin-dimer interface as well. MAP4, consisting of five repeats, further folds and accumulates above the intertubulin-dimer interface, interfering with kinesin-1 movement. Therefore, these cryo-EM studies reveal new insight into the structural basis of microtubule stabilization and inhibition of kinesin motility by the Tau family MAPs.

PMID:
30275105
PMCID:
PMC6279373
[Available on 2019-06-03]
DOI:
10.1083/jcb.201711182

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