Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates
Abstract The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligase...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05602-7 |
| _version_ | 1797414233770557440 |
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| author | Da Eun Jeong Hye Seon Lee Bonsu Ku Cheol-Hee Kim Seung Jun Kim Ho-Chul Shin |
| author_facet | Da Eun Jeong Hye Seon Lee Bonsu Ku Cheol-Hee Kim Seung Jun Kim Ho-Chul Shin |
| author_sort | Da Eun Jeong |
| collection | DOAJ |
| description | Abstract The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligases of the UBR subfamily recognize and degrade N-degrons through the ubiquitin-proteasome system. Herein, we investigated UBR4, which has a distinct mechanism for recognizing type-2 N-degrons. Structural analysis revealed that the UBR box of UBR4 differs from other UBR boxes in the N-degron binding sites. It recognizes type-2 N-terminal amino acids containing an aromatic ring and type-1 N-terminal arginine through two phenylalanines on its hydrophobic surface. We also characterized the binding mechanism for the second ligand residue. This is the report on the structural basis underlying the recognition of type-2 N-degrons by the UBR box with implications for understanding the N-end rule pathway. |
| first_indexed | 2024-03-09T05:30:07Z |
| format | Article |
| id | doaj.art-4800e1d332b54425963b351ee3b2552f |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-09T05:30:07Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-4800e1d332b54425963b351ee3b2552f2023-12-03T12:33:14ZengNature PortfolioCommunications Biology2399-36422023-11-016111410.1038/s42003-023-05602-7Insights into the recognition mechanism in the UBR box of UBR4 for its specific substratesDa Eun Jeong0Hye Seon Lee1Bonsu Ku2Cheol-Hee Kim3Seung Jun Kim4Ho-Chul Shin5Critical Disease Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Disease Target Structure Research Center, Division of Biomedical Research, KRIBBDisease Target Structure Research Center, Division of Biomedical Research, KRIBBDepartment of Bioscience & Biotechnology, Chungnam National UniversityCritical Disease Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Critical Disease Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Abstract The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligases of the UBR subfamily recognize and degrade N-degrons through the ubiquitin-proteasome system. Herein, we investigated UBR4, which has a distinct mechanism for recognizing type-2 N-degrons. Structural analysis revealed that the UBR box of UBR4 differs from other UBR boxes in the N-degron binding sites. It recognizes type-2 N-terminal amino acids containing an aromatic ring and type-1 N-terminal arginine through two phenylalanines on its hydrophobic surface. We also characterized the binding mechanism for the second ligand residue. This is the report on the structural basis underlying the recognition of type-2 N-degrons by the UBR box with implications for understanding the N-end rule pathway.https://doi.org/10.1038/s42003-023-05602-7 |
| spellingShingle | Da Eun Jeong Hye Seon Lee Bonsu Ku Cheol-Hee Kim Seung Jun Kim Ho-Chul Shin Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates Communications Biology |
| title | Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates |
| title_full | Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates |
| title_fullStr | Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates |
| title_full_unstemmed | Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates |
| title_short | Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates |
| title_sort | insights into the recognition mechanism in the ubr box of ubr4 for its specific substrates |
| url | https://doi.org/10.1038/s42003-023-05602-7 |
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