| RRC ID |
76302
|
| 著者 |
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.
|
| タイトル |
Structural model of microtubule dynamics inhibition by kinesin-4 from the crystal structure of KLP-12 -tubulin complex.
|
| ジャーナル |
Elife
|
| 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 the 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.
|
| 巻・号 |
11
|
| 公開日 |
2022-9-6
|
| DOI |
10.7554/eLife.77877
|
| PII |
77877
|
| PMID |
36065637
|
| PMC |
PMC9451533
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Kinesins*
Microtubules / metabolism
Models, Structural
Tubulin* / metabolism
|
| リソース情報 |
| 線虫 |
tm5176
tm10890 |
