Mechanism of Catalytic Microtubule Depolymerization via KIF2-Tubulin Transitional Conformation

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): Tadayuki Ogawa, Shinya Saijo, Nobutaka Shimizu, Xuguang Jiang, Nobutaka Hirokawa
Microtubules (MTs) are dynamic structures that are fundamental for cell morphogenesis and motility. MT-associated motors work efficiently to perform their functions. Unlike other motile kinesins, KIF2 catalytically depolymerizes MTs from the peeled protofilament end during ATP hydrolysis. However, the detailed mechanism by which KIF2 drives processive MT depolymerization remains unknown. To elucidate the catalytic mechanism, the transitional KIF2-tubulin complex during MT depolymerization was analyzed through multiple methods, including atomic force microscopy, size-exclusion chromatography, multi-angle light scattering, small-angle X-ray scattering, analytical ultracentrifugation, and mass spectrometry. The analyses outlined the conformation in which one KIF2core domain binds tightly to two tubulin dimers in the middle pre-hydrolysis state during ATP hydrolysis, a process critical for catalytic MT depolymerization. The X-ray crystallographic structure of the KIF2core domain displays the activated conformation that sustains the large KIF2-tubulin 1:2 complex.

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Teaser

Ogawa et al. reveal the mechanism of catalytic microtubule depolymerization by the microtubule-destabilizing kinesin, KIF2. They characterize the transitional conformation of the large KIF2-tubulin dimer 1:2 complex in solution, which is critical for the efficient mechanism of depolymerization at peeled microtubule protofilament ends during ATP hydrolysis.


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