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 20
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.