7LFF

Crystal structure of the Candida albicans kinesin-8 motor domain

Summary for 7LFF

• Entry DOI: 10.2210/pdb7lff/pdb
• Descriptor: Kinesin-like protein, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: kinesin, microtubule, depolymerase, motility, cytoskeleton, motor protein
• Biological source: Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
• Total number of polymer chains: 2
• Total formula weight: 99599.39

Authors

Allingham, J.S.,Hunter, B. (deposition date: 2021-01-16, release date: 2022-02-09, Last modification date: 2023-10-18)

Primary citation

Hunter, B.,Benoit, M.P.M.H.,Asenjo, A.B.,Doubleday, C.,Trofimova, D.,Frazer, C.,Shoukat, I.,Sosa, H.,Allingham, J.S.
Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape.
Nat Commun, 13:4198-4198, 2022

PubMed Abstract: 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.

PubMed: 35859148
DOI: 10.1038/s41467-022-31794-3

Experimental method

X-RAY DIFFRACTION (2.01 Å)