Document Details

Document Type : Article In Journal 
Document Title :
X-ray and Cryo-EM structures reveal mutual conformational changes of Kinesin and GTP-state microtubules upon binding
X-ray and Cryo-EM structures reveal mutual conformational changes of Kinesin and GTP-state microtubules upon binding
 
Document Language : English 
Abstract : The molecular motor kinesin moves along microtubules using energy from ATP hydrolysis in an initial step coupled with ADP release. In neurons, kinesin-1/KIF5C preferentially binds to the GTP-state microtubules over GDP-state microtubules to selectively enter an axon among many processes; however, because the atomic structure of nucleotide-free KIF5C is unavailable, its molecular mechanism remains unresolved. Here, the crystal structure of nucleotide-free KIF5C and the cryo-electron microscopic structure of nucleotide-free KIF5C complexed with the GTP-state microtubule are presented. The structures illustrate mutual conformational changes induced by interaction between the GTP-state microtubule and KIF5C. KIF5C acquires the 'rigor conformation', where mobile switches I and II are stabilized through L11 and the initial portion of the neck-linker, facilitating effective ADP release and the weak-to-strong transition of KIF5C microtubule affinity. Conformational changes to tubulin strengthen the longitudinal contacts of the GTP-state microtubule in a similar manner to GDP-taxol microtubules. These results and functional analyses provide the molecular mechanism of the preferential binding of KIF5C to GTP-state microtubules. 
ISSN : 1460-2075 
Journal Name : EMBO J 
Volume : 34 
Issue Number : 9 
Publishing Year : 1436 AH
2015 AD 
Article Type : Article 
Added Date : Tuesday, April 26, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Manatsu MorikawaMorikawa, Manatsu Investigator  
Hiroaki YajimaYajima, Hiroaki Researcher  
Ryo NittaNitta, Ryo Researcher  
Shigeyuki InoueInoue, Shigeyuki Researcher  
Toshihiko OguraOgura, Toshihiko Researcher  
Chikara SatoSato, Chikara Researcher  
Nobutaka HirokawaHirokawa, Nobutaka Researcher hirokawa@m.u-tokyo.ac.jp

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