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TitleMotility and microtubule depolymerization mechanisms of the Kinesin-8 motor, KIF19A.
Journal, issue, pagesElife, Vol. 5, Year 2016
Publish dateSep 30, 2016
AuthorsDoudou Wang / Ryo Nitta / Manatsu Morikawa / Hiroaki Yajima / Shigeyuki Inoue / Hideki Shigematsu / Masahide Kikkawa / Nobutaka Hirokawa /
PubMed AbstractThe kinesin-8 motor, KIF19A, accumulates at cilia tips and controls cilium length. Defective KIF19A leads to hydrocephalus and female infertility because of abnormally elongated cilia. Uniquely among ...The kinesin-8 motor, KIF19A, accumulates at cilia tips and controls cilium length. Defective KIF19A leads to hydrocephalus and female infertility because of abnormally elongated cilia. Uniquely among kinesins, KIF19A possesses the dual functions of motility along ciliary microtubules and depolymerization of microtubules. To elucidate the molecular mechanisms of these functions we solved the crystal structure of its motor domain and determined its cryo-electron microscopy structure complexed with a microtubule. The features of KIF19A that enable its dual function are clustered on its microtubule-binding side. Unexpectedly, a destabilized switch II coordinates with a destabilized L8 to enable KIF19A to adjust to both straight and curved microtubule protofilaments. The basic clusters of L2 and L12 tether the microtubule. The long L2 with a characteristic acidic-hydrophobic-basic sequence effectively stabilizes the curved conformation of microtubule ends. Hence, KIF19A utilizes multiple strategies to accomplish the dual functions of motility and microtubule depolymerization by ATP hydrolysis.
External linksElife / PubMed:27690357 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution2.72 - 7.0 Å
Structure data

9538

5gsy

EMDB-9538, PDB-5gsy:
Kinesin-8 motor, KIF19A, in the nucleotide-free state complexed with GDP-taxol microtubule
Method: EM (helical sym.) / Resolution: 7.0 Å

PDB-5gsz:
Crystal Structure of the KIF19A Motor Domain Complexed with Mg-ADP
Method: X-RAY DIFFRACTION / Resolution: 2.72 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • mus musculus (house mouse)
KeywordsMOTOR PROTEIN / Kinesin-8 / KIF19A / GDP-taxol-microtubule / Plus-end directed motor / Microtubule depolymerization / kinesin / motor domain / Mg-ADP

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