Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules

ELife
Daifei LiuCharles V Sindelar

Abstract

The detailed basis of walking by dimeric molecules of kinesin along microtubules has remained unclear, partly because available structural methods have been unable to capture microtubule-bound intermediates of this process. Utilizing novel electron cryomicroscopy methods, we solved structures of microtubule-attached, dimeric kinesin bound to an ATP analog. We find that under these conditions, the kinesin dimer can attach to the microtubule with either one or two motor domains, and we present sub-nanometer resolution reconstructions of both states. The former structure reveals a novel kinesin conformation that revises the current understanding of how ATP binding is coupled to forward stepping of the motor. The latter structure indicates how tension between the two motor domains keeps their cycles out of phase in order to stimulate directional motility. The methods presented here pave the way for future structural studies of a variety of challenging macromolecules that bind to microtubules and other filaments.

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Citations

Feb 16, 2018·The Journal of Biological Chemistry·Susan P GilbertIvan Rayment
Feb 22, 2018·The Journal of Biological Chemistry·Andrew HuehnCharles V Sindelar
May 31, 2018·The Journal of Biological Chemistry·Kellie A WollRoderic G Eckenhoff
Apr 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Bojan MilicSteven M Block
Jun 17, 2021·Nature Communications·Matthieu P M H BenoitHernando Sosa

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Methods Mentioned

BETA
gel filtration

Software Mentioned

FREALIGN
Chimera
SPIDER
FINDKIN
SerialEM

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