Sabrina Habisov, Jessica Huber, Yoshinobu Ichimura, Masato Akutsu, Natalia Rogova, Frank Löhr, David G. McEwan, Terje Johansen, Ivan Đikić, Volker Dötsch, Masaaki Komatsu, Vladimir V. Rogov, Vladimir Kirkin
- The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifier-conjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway.
MetadatenVerfasserangaben: | Sabrina Habisov, Jessica HuberORCiDGND, Yoshinobu Ichimura, Masato AkutsuORCiD, Natalia Rogova, Frank LöhrORCiD, David G. McEwanORCiD, Terje JohansenORCiD, Ivan ĐikićORCiDGND, Volker DötschORCiDGND, Masaaki KomatsuORCiD, Vladimir V. RogovORCiDGND, Vladimir KirkinORCiD |
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URN: | urn:nbn:de:hebis:30:3-772658 |
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DOI: | https://doi.org/10.1074/jbc.M116.715474 |
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ISSN: | 0021-9258 |
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Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/26929408 |
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Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
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Verlag: | American Society for Biochemistry and Molecular Biology Publications |
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Verlagsort: | Bethesda, Md |
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Dokumentart: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Veröffentlichung (online): | 04.01.2021 |
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Jahr der Erstveröffentlichung: | 2016 |
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Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Datum der Freischaltung: | 06.03.2024 |
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Freies Schlagwort / Tag: | LC3/GABARAP; LIR; UBA5; UFIM; UFM1; isothermal titration calorimetry (ITC); nuclear magnetic resonance (NMR); protein motif; signal transduction; x-ray crystallography |
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Jahrgang: | 291.2016 |
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Ausgabe / Heft: | 17 |
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Seitenzahl: | 17 |
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Erste Seite: | 9025 |
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Letzte Seite: | 9041 |
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Institute: | Biochemie, Chemie und Pharmazie |
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| Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Sammlungen: | Universitätspublikationen |
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Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |
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