ORCID: https://orcid.org/0000-0001-8270-1449; Waldmann, Herbert; Raunser, Stefan and Musacchio, Andrea
(2017):
Structure of the RZZ complex and molecular basis of its interaction with Spindly.
In: Journal of Cell Biology, Vol. 216, No. 4: pp. 961-981
Abstract
Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific approximate to 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 alpha beta'epsilon-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.
Item Type: | Journal article |
---|---|
Faculties: | Chemistry and Pharmacy > Department of Biochemistry |
Subjects: | 500 Science > 540 Chemistry |
ISSN: | 0021-9525 |
Language: | English |
Item ID: | 54142 |
Date Deposited: | 14. Jun 2018, 09:55 |
Last Modified: | 08. Jun 2021, 05:14 |