PT  - JOURNAL ARTICLE
AU  - Shinya Taguchi
AU  - Juri Nakano
AU  - Tsuyoshi Imasaki
AU  - Tomoki Kita
AU  - Yumiko Saijo-Hamano
AU  - Naoki Sakai
AU  - Hideki Shigematsu
AU  - Hiromichi Okuma
AU  - Takahiro Shimizu
AU  - Eriko Nitta
AU  - Satoshi Kikkawa
AU  - Satoshi Mizobuchi
AU  - Shinsuke Niwa
AU  - Ryo Nitta
TI  - Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 –tubulin complex
AID  - 10.1101/2022.02.14.480441
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.14.480441
4099  - http://biorxiv.org/content/early/2022/02/15/2022.02.14.480441.short
4100  - http://biorxiv.org/content/early/2022/02/15/2022.02.14.480441.full
AB  - Kinesin superfamily proteins are microtubule-based molecular motors driven by the energy of ATP hydrolysis. Among them, the kinesin-4 family is a unique motor that inhibits microtubule dynamics. Although mutations of kinesin-4 cause several diseases, its molecular mechanism is unclear because of the difficulty of visualizing the high-resolution structure of kinesin-4 working at the microtubule plus-end. Here, we report that KLP-12, a C. elegans kinesin-4 ortholog of KIF21A and KIF21B, is essential for proper length control of C. elegans axons, and its motor domain represses microtubule polymerization in vitro. The crystal structure of the KLP-12 motor domain complexed with tubulin, which represents the high-resolution structural snapshot of inhibition state of microtubule-end dynamics, revealed the bending effect of KLP-12 for tubulin. Comparison with the KIF5B-tubulin and KIF2C-tubulin complexes, which represent the elongation and shrinking forms of microtubule ends, respectively, showed the curvature of tubulin introduced by KLP-12 is in between them. Taken together, KLP-12 controls the proper length of axons by modulating the curvature of the microtubule ends to inhibit the microtubule dynamics.Competing Interest StatementThe authors have declared no competing interest.