TY - JOUR TI - Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins AU - Atherton, Joseph AU - Farabella, Irene AU - Yu, I-Mei AU - Rosenfeld, Steven S AU - Houdusse, Anne AU - Topf, Maya AU - Moores, Carolyn A A2 - Hyman, Anthony A VL - 3 PY - 2014 DA - 2014/09/10 SP - e03680 C1 - eLife 2014;3:e03680 DO - 10.7554/eLife.03680 UR - https://doi.org/10.7554/eLife.03680 AB - Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles—including their nucleotide-free states—at ∼7 Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin–microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface. KW - microtubule KW - kinesin KW - cryo-electron microscopy KW - motor KW - cytoskeleton KW - ATPase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -