Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.
Multi-subunit Cullin-RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-contai...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797061853483892736 |
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| author | Muniz, JR Guo, K Kershaw, N Ayinampudi, V von Delft, F Babon, J Bullock, A |
| author_facet | Muniz, JR Guo, K Kershaw, N Ayinampudi, V von Delft, F Babon, J Bullock, A |
| author_sort | Muniz, JR |
| collection | OXFORD |
| description | Multi-subunit Cullin-RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-containing ankyrin repeat proteins (ASB1-18), which assemble with Elongins B and C and Cul5. We determined the crystal structures of the ternary complex of ASB9-Elongin B/C as well as the interacting N-terminal domain of Cul5 and used structural comparisons to establish a model for the complete Cul5-based E3 ligase. The structures reveal a distinct architecture of the ASB9 complex that positions the ankyrin domain coaxial to the SOCS box-Elongin B/C complex and perpendicular to other repeat protein complexes. This alternative architecture appears favorable to present the ankyrin domain substrate-binding site to the E2-ubiquitin, while also providing spacing suitable for bulky ASB9 substrates, such as the creatine kinases. The presented Cul5 structure also differs from previous models and deviates from other Cullins via a rigid-body rotation between Cullin repeats. This work highlights the adaptability of repeat domain proteins as scaffolds in substrate recognition and lays the foundation for future structure-function studies of this important E3 family. |
| first_indexed | 2024-03-06T20:37:06Z |
| format | Journal article |
| id | oxford-uuid:33031264-5ed5-414d-a8ed-3734ac75ef38 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:37:06Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:33031264-5ed5-414d-a8ed-3734ac75ef382022-03-26T13:17:36ZMolecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:33031264-5ed5-414d-a8ed-3734ac75ef38EnglishSymplectic Elements at Oxford2013Muniz, JRGuo, KKershaw, NAyinampudi, Vvon Delft, FBabon, JBullock, AMulti-subunit Cullin-RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-containing ankyrin repeat proteins (ASB1-18), which assemble with Elongins B and C and Cul5. We determined the crystal structures of the ternary complex of ASB9-Elongin B/C as well as the interacting N-terminal domain of Cul5 and used structural comparisons to establish a model for the complete Cul5-based E3 ligase. The structures reveal a distinct architecture of the ASB9 complex that positions the ankyrin domain coaxial to the SOCS box-Elongin B/C complex and perpendicular to other repeat protein complexes. This alternative architecture appears favorable to present the ankyrin domain substrate-binding site to the E2-ubiquitin, while also providing spacing suitable for bulky ASB9 substrates, such as the creatine kinases. The presented Cul5 structure also differs from previous models and deviates from other Cullins via a rigid-body rotation between Cullin repeats. This work highlights the adaptability of repeat domain proteins as scaffolds in substrate recognition and lays the foundation for future structure-function studies of this important E3 family. |
| spellingShingle | Muniz, JR Guo, K Kershaw, N Ayinampudi, V von Delft, F Babon, J Bullock, A Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title | Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title_full | Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title_fullStr | Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title_full_unstemmed | Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title_short | Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases. |
| title_sort | molecular architecture of the ankyrin socs box family of cul5 dependent e3 ubiquitin ligases |
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