Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape.

Autor: Hunter, Byron, Benoit, Matthieu P. M. H., Asenjo, Ana B., Doubleday, Caitlin, Trofimova, Daria, Frazer, Corey, Shoukat, Irsa, Sosa, Hernando, Allingham, John S.
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Zdroj: Nature Communications; 7/20/2022, Vol. 13 Issue 1, p1-19, 19p
Abstrakt: Kinesin-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends, but their mechanism of combining these distinct activities remains unclear. We addressed this by obtaining cryo-EM structures (2.6–3.9 Å) of Candida albicans Kip3 in different catalytic states on the microtubule lattice and on a curved microtubule end mimic. We also determined a crystal structure of microtubule-unbound CaKip3-ADP (2.0 Å) and analyzed the biochemical activity of CaKip3 and kinesin-1 mutants. These data reveal that the microtubule depolymerization activity of kinesin-8 originates from conformational changes of its motor core that are amplified by dynamic contacts between its extended loop-2 and tubulin. On curved microtubule ends, loop-1 inserts into preceding motor domains, forming head-to-tail arrays of kinesin-8s that complement loop-2 contacts with curved tubulin and assist depolymerization. On straight tubulin protofilaments in the microtubule lattice, loop-2-tubulin contacts inhibit conformational changes in the motor core, but in the ADP-Pi state these contacts are relaxed, allowing neck-linker docking for motility. We propose that these tubulin shape-induced alternations between pro-microtubule-depolymerization and pro-motility kinesin states, regulated by loop-2, are the key to the dual activity of kinesin-8 motors. Kinesin-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends. This study shows how kinesin-8s alternate between a promotility and a pro-microtubule-depolymerization state via their tubulin shape-sensing loop-2 region. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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