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Structure of the RZZ complex and molecular basis of its interaction with Spindly

Abstract : 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.
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Shyamal Mosalaganti, Jenny Keller, Anika Altenfeld, Franz Herzog, Pascaline Rombaut, et al.. Structure of the RZZ complex and molecular basis of its interaction with Spindly. Journal of Cell Biology, Rockefeller University Press, 2017, 216 (4), pp.961-981. ⟨10.1083/jcb.201611060⟩. ⟨pasteur-02749286⟩

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