7TR3
CaKip3[2-482] - AMP-PNP in complex with a dolastatin-10-stabilized tubulin ring
Summary for 7TR3
| Entry DOI | 10.2210/pdb7tr3/pdb |
| EMDB information | 26080 |
| Descriptor | Tubulin alpha-1B chain, Tubulin beta-2B chain, Kinesin-like protein, ... (8 entities in total) |
| Functional Keywords | kip3, kinesin, tubulin, dolastatin-10, motor protein |
| Biological source | Candida albicans More |
| Total number of polymer chains | 3 |
| Total formula weight | 157355.77 |
| Authors | Benoit, M.P.M.H.,Asenjo, A.B.,Hunter, B.,Allingham, J.S.,Sosa, H. (deposition date: 2022-01-27, release date: 2022-07-20, 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 Cited by 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: 35859148DOI: 10.1038/s41467-022-31794-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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