TY - JOUR
T1 - Structural Basis of Backwards Motion in Kinesin-1-Kinesin-14 Chimera
T2 - Implication for Kinesin-14 Motility
AU - Yamagishi, Masahiko
AU - Shigematsu, Hideki
AU - Yokoyama, Takeshi
AU - Kikkawa, Masahide
AU - Sugawa, Mitsuhiro
AU - Aoki, Mari
AU - Shirouzu, Mikako
AU - Yajima, Junichiro
AU - Nitta, Ryo
N1 - Funding Information:
We thank N. Ohsawa, Y. Tomabechi, and Y. Maruyama for technical assistance, and N. Sakai for useful discussions. We are grateful to F. Sigworth for critical reading of the manuscript. This work was supported in part by JSPS KAKENHI ( 15H01656 to H.S., 15H01629 and 15K07022 to J.Y., and 15K08168 to R.N.), by Platform for Dynamic Approaches to Living Systems from MEXT (to J.Y.), and by Takeda Science Foundation (to R.N.).
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/8/2
Y1 - 2016/8/2
N2 - Kinesin-14 is a unique minus-end-directed microtubule-based motor. A swinging motion of a class-specific N-terminal neck helix has been proposed to produce minus-end directionality. However, it is unclear how swinging of the neck helix is driven by ATP hydrolysis utilizing the highly conserved catalytic core among all kinesins. Here, using a motility assay, we show that in addition to the neck helix, the conserved five residues at the C-terminal region in kinesin-14, namely the neck mimic, are necessary to give kinesin-1 an ability to reverse its directionality toward the minus end of microtubules. Our structural analyses further demonstrate that the C-terminal neck mimic, in cooperation with conformational changes in the catalytic core during ATP binding, forms a kinesin-14 bundle with the N-terminal neck helix to swing toward the minus end of microtubules. Thus, the neck mimic plays a crucial role in coupling the chemical ATPase reaction with the mechanical cycle to produce the minus-end-directed motility of kinesin-14.
AB - Kinesin-14 is a unique minus-end-directed microtubule-based motor. A swinging motion of a class-specific N-terminal neck helix has been proposed to produce minus-end directionality. However, it is unclear how swinging of the neck helix is driven by ATP hydrolysis utilizing the highly conserved catalytic core among all kinesins. Here, using a motility assay, we show that in addition to the neck helix, the conserved five residues at the C-terminal region in kinesin-14, namely the neck mimic, are necessary to give kinesin-1 an ability to reverse its directionality toward the minus end of microtubules. Our structural analyses further demonstrate that the C-terminal neck mimic, in cooperation with conformational changes in the catalytic core during ATP binding, forms a kinesin-14 bundle with the N-terminal neck helix to swing toward the minus end of microtubules. Thus, the neck mimic plays a crucial role in coupling the chemical ATPase reaction with the mechanical cycle to produce the minus-end-directed motility of kinesin-14.
UR - http://www.scopus.com/inward/record.url?scp=84979976469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979976469&partnerID=8YFLogxK
U2 - 10.1016/j.str.2016.05.021
DO - 10.1016/j.str.2016.05.021
M3 - Article
C2 - 27452403
AN - SCOPUS:84979976469
VL - 24
SP - 1322
EP - 1334
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 8
ER -