6TA3
Human kinesin-5 motor domain in the GSK-1 state bound to microtubules (Conformation 1)
Summary for 6TA3
| Entry DOI | 10.2210/pdb6ta3/pdb |
| EMDB information | 10421 |
| Descriptor | Tubulin beta chain, Tubulin alpha-1B chain, Kinesin-like protein KIF11, ... (6 entities in total) |
| Functional Keywords | kinesin, microtubule, mitosis, inhibition, motor, cell cycle |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 142003.00 |
| Authors | Pena, A.,Sweeney, A.,Cook, A.D.,Moores, C.A.,Topf, M. (deposition date: 2019-10-29, release date: 2020-04-22, Last modification date: 2025-04-09) |
| Primary citation | Pena, A.,Sweeney, A.,Cook, A.D.,Topf, M.,Moores, C.A. Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy. Structure, 28:450-457.e5, 2020 Cited by PubMed Abstract: Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric human kinesin-5 ATPase and microtubule gliding activities, and promotes the motor's microtubule stabilization activity. Using cryoelectron microscopy, we determined the 3D structure of the microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The structure reveals that GSK-1 stabilizes the microtubule binding surface of the motor in an ATP-like conformation, while destabilizing regions of the motor around the empty nucleotide binding pocket. Density corresponding to GSK-1 is located between helix-α4 and helix-α6 in the motor domain at its interface with the microtubule. Using a combination of difference mapping and protein-ligand docking, we characterized the kinesin-5-GSK-1 interaction and further validated this binding site using mutagenesis. This work opens up new avenues of investigation of kinesin inhibition and spindle perturbation. PubMed: 32084356DOI: 10.1016/j.str.2020.01.013 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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