Conformational plasticity of the ULK3 kinase domain
The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhib...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Portland Press
2021
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| _version_ | 1826307919295021056 |
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| author | Mathea, S Salah, E Tallant, C Chatterjee, D Berger, B-T Konietzny, R Müller-Knapp, S Kessler, BM Knapp, S |
| author_facet | Mathea, S Salah, E Tallant, C Chatterjee, D Berger, B-T Konietzny, R Müller-Knapp, S Kessler, BM Knapp, S |
| author_sort | Mathea, S |
| collection | OXFORD |
| description | The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.
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| first_indexed | 2024-03-07T07:10:17Z |
| format | Journal article |
| id | oxford-uuid:1b7a3d3a-13b9-41d7-be15-bcb5832a7e7f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:10:17Z |
| publishDate | 2021 |
| publisher | Portland Press |
| record_format | dspace |
| spelling | oxford-uuid:1b7a3d3a-13b9-41d7-be15-bcb5832a7e7f2022-06-30T08:51:30ZConformational plasticity of the ULK3 kinase domainJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1b7a3d3a-13b9-41d7-be15-bcb5832a7e7fEnglishSymplectic ElementsPortland Press2021Mathea, SSalah, ETallant, CChatterjee, DBerger, B-TKonietzny, RMüller-Knapp, SKessler, BMKnapp, SThe human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein. |
| spellingShingle | Mathea, S Salah, E Tallant, C Chatterjee, D Berger, B-T Konietzny, R Müller-Knapp, S Kessler, BM Knapp, S Conformational plasticity of the ULK3 kinase domain |
| title | Conformational plasticity of the ULK3 kinase domain |
| title_full | Conformational plasticity of the ULK3 kinase domain |
| title_fullStr | Conformational plasticity of the ULK3 kinase domain |
| title_full_unstemmed | Conformational plasticity of the ULK3 kinase domain |
| title_short | Conformational plasticity of the ULK3 kinase domain |
| title_sort | conformational plasticity of the ulk3 kinase domain |
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