TY - JOUR TI - Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules AU - Scarborough, Emily Anne AU - Davis, Trisha N AU - Asbury, Charles L A2 - Cheeseman, Iain M A2 - Akhmanova, Anna A2 - Cheeseman, Iain M VL - 8 PY - 2019 DA - 2019/05/02 SP - e44489 C1 - eLife 2019;8:e44489 DO - 10.7554/eLife.44489 UR - https://doi.org/10.7554/eLife.44489 AB - Regulation of the outer kinetochore complex Ndc80 is essential to ensure correct kinetochore-microtubule attachments during mitosis. Here, we present a novel mechanism of regulation that is intrinsic to its structure; tight bending of the Ndc80 complex inhibits its microtubule binding. Using single molecule Förster resonance energy transfer (FRET), we show that the Saccharomyces cerevisiae Ndc80 complex can fluctuate between straight and bent forms, and that binding of the complex to microtubules selects for straightened forms. The loop region of the complex enables its bent conformation, as deletion of the loop promotes straightening. In addition, the kinetochore complex MIND enhances microtubule binding by opposing the tightly bent, auto-inhibited conformation of the Ndc80 complex. We suggest that prior to its assembly at the kinetochore, the Ndc80 complex interchanges between bent (auto-inhibited) and open conformations. Once assembled, its association with MIND stabilizes the Ndc80 complex in a straightened form for higher affinity microtubule binding. KW - kinetochore KW - microtubule KW - mitosis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -