Structural basis for mitotic centrosome assembly in flies
In flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved Leucine Zipper (LZ) and Cnn-Motif 2 (CM2) domains that co-assemble into a 2:2 c...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
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Cell Press
2017
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| _version_ | 1826291125827141632 |
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| author | Feng, Z Caballe, A Wainman, A Johnson, S Haensele, A Cottee, M Conduit, P Lea, S Raff, J |
| author_facet | Feng, Z Caballe, A Wainman, A Johnson, S Haensele, A Cottee, M Conduit, P Lea, S Raff, J |
| author_sort | Feng, Z |
| collection | OXFORD |
| description | In flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved Leucine Zipper (LZ) and Cnn-Motif 2 (CM2) domains that co-assemble into a 2:2 complex in vitro. We solve the crystal structure of the LZ:CM2 complex, revealing that both proteins form helical dimers that assemble into an unusual tetramer. A slightly longer version of the LZ can form micron-scale structures with CM2, whose assembly is stimulated by Plk1 phosphorylation in vitro. Mutating individual residues that perturb LZ:CM2 tetramer assembly perturbs the formation of these micron-scale assemblies in vitro and Cnn scaffold assembly in vivo. Thus, Cnn molecules have an intrinsic ability to form large, LZ:CM2-interaction-dependent assemblies that are critical for mitotic centrosome assembly. These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly. |
| first_indexed | 2024-03-07T02:54:42Z |
| format | Journal article |
| id | oxford-uuid:aee04199-6bc2-4564-8b26-7241ed300419 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:54:42Z |
| publishDate | 2017 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:aee04199-6bc2-4564-8b26-7241ed3004192022-03-27T03:45:46ZStructural basis for mitotic centrosome assembly in fliesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aee04199-6bc2-4564-8b26-7241ed300419Symplectic Elements at OxfordCell Press2017Feng, ZCaballe, AWainman, AJohnson, SHaensele, ACottee, MConduit, PLea, SRaff, JIn flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved Leucine Zipper (LZ) and Cnn-Motif 2 (CM2) domains that co-assemble into a 2:2 complex in vitro. We solve the crystal structure of the LZ:CM2 complex, revealing that both proteins form helical dimers that assemble into an unusual tetramer. A slightly longer version of the LZ can form micron-scale structures with CM2, whose assembly is stimulated by Plk1 phosphorylation in vitro. Mutating individual residues that perturb LZ:CM2 tetramer assembly perturbs the formation of these micron-scale assemblies in vitro and Cnn scaffold assembly in vivo. Thus, Cnn molecules have an intrinsic ability to form large, LZ:CM2-interaction-dependent assemblies that are critical for mitotic centrosome assembly. These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly. |
| spellingShingle | Feng, Z Caballe, A Wainman, A Johnson, S Haensele, A Cottee, M Conduit, P Lea, S Raff, J Structural basis for mitotic centrosome assembly in flies |
| title | Structural basis for mitotic centrosome assembly in flies |
| title_full | Structural basis for mitotic centrosome assembly in flies |
| title_fullStr | Structural basis for mitotic centrosome assembly in flies |
| title_full_unstemmed | Structural basis for mitotic centrosome assembly in flies |
| title_short | Structural basis for mitotic centrosome assembly in flies |
| title_sort | structural basis for mitotic centrosome assembly in flies |
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