TY - JOUR TI - The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry AU - Atherton, Joseph AU - Yu, I-Mei AU - Cook, Alexander AU - Muretta, Joseph M AU - Joseph, Agnel AU - Major, Jennifer AU - Sourigues, Yannick AU - Clause, Jeffrey AU - Topf, Maya AU - Rosenfeld, Steven S AU - Houdusse, Anne AU - Moores, Carolyn A A2 - Egelman, Edward H VL - 6 PY - 2017 DA - 2017/08/11 SP - e27793 C1 - eLife 2017;6:e27793 DO - 10.7554/eLife.27793 UR - https://doi.org/10.7554/eLife.27793 AB - MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) and size (~40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function. KW - cryo-electron microscopy KW - kinesins KW - mechanochemistry KW - microtubules KW - mitosis KW - ATPase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -