7TR2

Apo CaKip3[2-436]-L2-mutant(HsKHC) in complex with a microtubule

Summary for 7TR2

• Entry DOI: 10.2210/pdb7tr2/pdb
• EMDB information: 26079
• Descriptor: Kinesin-like protein,Kinesin-1 heavy chain, Tubulin alpha-1B chain, Tubulin beta-2B chain, ... (7 entities in total)
• Functional Keywords: kip3, kinesin, motility, microtubule, tubulin, motor protein
• Biological source: Candida albicans; More
• Total number of polymer chains: 3
• Total formula weight: 148393.79

Authors

Benoit, M.P.M.H.,Asenjo, A.B.,Hunter, B.,Allingham, J.S.,Sosa, H. (deposition date: 2022-01-27, release date: 2022-07-13, Last modification date: 2024-02-21)

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

ELECTRON MICROSCOPY (3 Å)