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Journal articles
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.
Cited literature [98 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-02749286
Contributor : Anne Marie Wehenkel <>
Submitted on : Wednesday, June 3, 2020 - 3:07:57 PM
Last modification on : Wednesday, June 17, 2020 - 3:07:44 AM
Long-term archiving on: : Thursday, December 3, 2020 - 7:00:50 AM
Contributor : Anne Marie Wehenkel <>
Submitted on : Wednesday, June 3, 2020 - 3:07:57 PM
Last modification on : Wednesday, June 17, 2020 - 3:07:44 AM
Long-term archiving on: : Thursday, December 3, 2020 - 7:00:50 AM
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Structure of the RZZ complex a...
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