Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 - tubulin complex

Taguchi, S.; Nakano, J.; Imasaki, T.; Kita, T.; Saijo-Hamano, Y.; Sakai, N.; Shigematsu, H.; Okuma, H.; Shimizu, T.; Nitta, E.; Kikkawa, S.; Mizobuchi, S.; Niwa, S.; Nitta, R.

doi:10.1101/2022.02.14.480441

bioRxiv · 10.1101/2022.02.14.480441

Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 - tubulin complex

Taguchi, S.·Nakano, J.·Imasaki, T.·Kita, T.·Saijo-Hamano, Y.·Sakai, N.·Shigematsu, H.·Okuma, H.·Shimizu, T.·Nitta, E.·Kikkawa, S.·Mizobuchi, S.·Niwa, S.·Nitta, R.

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Abstract

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.

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Taguchi, S., Nakano, J., Imasaki, T., Kita, T., Saijo-Hamano, Y., Sakai, N., Shigematsu, H., Okuma, H., Shimizu, T., Nitta, E., Kikkawa, S., Mizobuchi, S., Niwa, S., Nitta, R.. 2022-02-15. Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 - tubulin complex. https://doi.org/10.1101/2022.02.14.480441

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