PT - JOURNAL ARTICLE AU - Mosalaganti, Shyamal AU - Keller, Jenny AU - Altenfeld, Anika AU - Winzker, Michael AU - Rombaut, Pascaline AU - Saur, Michael AU - Petrovic, Arsen AU - Wehenkel, Annemarie AU - Wohlgemuth, Sabine AU - Müller, Franziska AU - Maffini, Stefano AU - Bange, Tanja AU - Herzog, Franz AU - Waldmann, Herbert AU - Raunser, Stefan AU - Musacchio, Andrea TI - Structure of the RZZ complex and molecular basis of its interaction with Spindly DP - 2017 Mar 18 TA - The Journal of Cell Biology 4099 - http://jcb.rupress.org/content/early/2017/03/17/jcb.201611060.short 4100 - http://jcb.rupress.org/content/early/2017/03/17/jcb.201611060.full AB - Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific ≈800-kD ROD–Zwilch–ZW10 (RZZ) complex builds a fibrous corona that assembles on mitotic kinetochores before MT attachment to promote chromosome alignment and robust spindle assembly checkpoint signaling. In this study, we combine biochemical reconstitutions, single-particle electron cryomicroscopy, cross-linking mass spectrometry, and structural modeling to build a complete model of human RZZ. We find that RZZ is structurally related to self-assembling cytosolic coat scaffolds that mediate membrane cargo trafficking, including Clathrin, Sec13–Sec31, and αβ’ε-COP. We show that Spindly, a dynein adaptor, is related to BicD2 and binds RZZ directly in a farnesylation-dependent but membrane-independent manner. Through a targeted chemical biology approach, we identify ROD as the Spindly farnesyl receptor. Our results suggest that RZZ is dynein’s cargo at human kinetochores.