6VPO

Cryo-EM structure of microtubule-bound KLP61F motor domain in the AMPPNP state

Summary for 6VPO

• Entry DOI: 10.2210/pdb6vpo/pdb
• EMDB information: 21314 21315
• Descriptor: Tubulin alpha-1A chain, Tubulin beta chain, Kinesin-like protein Klp61F, ... (7 entities in total)
• Functional Keywords: kinesin-5, microtubules, mitotic spindles, amppnp state, cell cycle, motor protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 144153.25

Authors

Bodrug, T.,Wilson-Kubalek, E.M.,Nithianantham, S.,Debs, G.,Sindelar, C.V.,Milligan, R.,Al-Bassam, J. (deposition date: 2020-02-04, release date: 2020-02-19, Last modification date: 2024-03-06)

Primary citation

Bodrug, T.,Wilson-Kubalek, E.M.,Nithianantham, S.,Thompson, A.F.,Alfieri, A.,Gaska, I.,Major, J.,Debs, G.,Inagaki, S.,Gutierrez, P.,Gheber, L.,McKenney, R.J.,Sindelar, C.V.,Milligan, R.,Stumpff, J.,Rosenfeld, S.S.,Forth, S.T.,Al-Bassam, J.
The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding.
Elife, 9:-, 2020

PubMed Abstract: Kinesin-5 motors organize mitotic spindles by sliding apart microtubules. They are homotetramers with dimeric motor and tail domains at both ends of a bipolar minifilament. Here, we describe a regulatory mechanism involving direct binding between tail and motor domains and its fundamental role in microtubule sliding. Kinesin-5 tails decrease microtubule-stimulated ATP-hydrolysis by specifically engaging motor domains in the nucleotide-free or ADP states. Cryo-EM reveals that tail binding stabilizes an open motor domain ATP-active site. Full-length motors undergo slow motility and cluster together along microtubules, while tail-deleted motors exhibit rapid motility without clustering. The tail is critical for motors to zipper together two microtubules by generating substantial sliding forces. The tail is essential for mitotic spindle localization, which becomes severely reduced in tail-deleted motors. Our studies suggest a revised microtubule-sliding model, in which kinesin-5 tails stabilize motor domains in the microtubule-bound state by slowing ATP-binding, resulting in high-force production at both homotetramer ends.

PubMed: 31958056
DOI: 10.7554/eLife.51131

Experimental method

ELECTRON MICROSCOPY (4.4 Å)