Structure of the RZZ complex and molecular basis of its interaction with Spindly
| Autor: | Sabine Wohlgemuth, Stefano Maffini, Herbert Waldmann, Michael Saur, Shyamal Mosalaganti, Jenny Keller, Pascaline Rombaut, Tanja Bange, Franz Herzog, Anika Altenfeld, Franziska Müller, Michael Winzker, Annemarie Wehenkel, Andrea Musacchio, Stefan Raunser, Arsen Petrovic |
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| Přispěvatelé: | Max Planck Institute of Molecular Physiology, Max-Planck-Gesellschaft, Ludwig-Maximilians-Universität München (LMU), Technische Universität Dortmund [Dortmund] (TU), Universität Duisburg-Essen [Essen], J. Keller acknowledges support by the European Molecular Biology Organization long-term fellowship ALTF 331-2010. A. Wehenkel acknowledges support by the European Molecular Biology Organization long-term fellowship ALTF 662-2008 and Marie Curie Intra-European Fellowship. A. Musacchio acknowledges funding by the European Research Council Advanced Grant RECEPIANCE (grant 669686) and the Deutsche Forschungsgemeinschaft Collaborative Research Centre (CRC) 1093. F. Herzog is supported by the European Research Council StG MolStruKT (grant 638218) and by the Deutsche Forschungsgemeinschaft (grant GRK1721). S. Raunser gratefully acknowledges the Max Planck Society and the European Council under the European Union’s Seventh Framework Programme (FP7/2007–2013, grant 615984)., We thank Marta Mattiuzzo and Anna De Antoni for sharing unpublished reagents, and we thank members of our laboratories for helpful discussions., European Project: 669686,H2020,ERC-2014-ADG,RECEPIANCE(2015), European Project: 638218,H2020,ERC-2014-STG,MolStruKT(2015), European Project: 615984,EC:FP7:ERC,ERC-2013-CoG,BACTERIAL SYRINGES(2014), Universität Duisburg-Essen = University of Duisburg-Essen [Essen] |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Cycle Proteins MESH: Spindle Apparatus / metabolism Microtubules MESH: Protein Transport / physiology MESH: Dyneins / metabolism MESH: Microtubules / metabolism Kinetochores Research Articles RZZ complex [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] biology Kinetochore MESH: Kinetochores / metabolism MESH: Cell Cycle Proteins / metabolism Cell biology Protein Transport Spindle checkpoint [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] MESH: M Phase Cell Cycle Checkpoints / physiology Microtubule-Associated Proteins MESH: Kinetochores / physiology Biologie endocrine system MESH: Cell Line Tumor Dynein Mitosis Spindle Apparatus MESH: Carrier Proteins / metabolism Clathrin Article 03 medical and health sciences MESH: Spindle Apparatus / physiology Dynein ATPase Cell Line Tumor Humans MESH: Microtubule-Associated Proteins / metabolism MESH: Humans MESH: Mitosis / physiology Dyneins Cell Biology Spindle apparatus 030104 developmental biology MESH: HeLa Cells biology.protein M Phase Cell Cycle Checkpoints Carrier Proteins HeLa Cells |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2017, 216 (4), pp.961-981. ⟨10.1083/jcb.201611060⟩ Journal of Cell Biology, 2017, 216 (4), pp.961-981. ⟨10.1083/jcb.201611060⟩ The Journal of Cell Biology |
| ISSN: | 0021-9525 1540-8140 |
| DOI: | 10.1083/jcb.201611060⟩ |
| Popis: | The Rod–Zw10–Zwilch (RZZ) complex assembles as a fibrous corona on kinetochores before microtubule attachment during mitotic spindle formation. Mosalaganti et al. provide new structural insight into the Spindly–RZZ complex that suggests that it resembles a dynein adaptor–cargo pair in the kinetochore corona. 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. |
| Databáze: | OpenAIRE |
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