A modular toolbox to generate complex polymeric ubiquitin architectures using orthogonal sortase enzymes
2021-11-11
Maximilian Fottner, Maria Weyh, Stefan Gaussmann, Dominic Schwarz, Michael Sattler, Kathrin Lang
Nat Commun., 2021, 12, 6515
The post-translational modification of proteins with ubiquitin (Ub) and Ub-like modifiers (Ubls) represents one of the most important regulators in eukaryotic biology. Polymeric Ub/Ubl chains of distinct topologies control the activity, stability, interaction and localization of almost all cellular proteins and elicit a variety of biological outputs. Our ability to characterize the roles of distinct Ub/Ubl topologies and to identify enzymes and receptors that create, recognize and remove these modifications is however hampered by the difficulty to prepare them. Here we introduce a modular toolbox (Ubl-tools) that allows the stepwise assembly of Ub/Ubl chains in a flexible and user-defined manner facilitated by orthogonal sortase enzymes. We demonstrate the universality and applicability of Ubl-tools by generating distinctly linked Ub/Ubl hybrid chains, and investigate their role in DNA damage repair. Importantly, Ubl-tools guarantees straightforward access to target proteins, site-specifically modified with distinct homo- and heterotypic (including branched) Ub chains, providing a powerful approach for studying the functional impact of these complex modifications on cellular processes.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
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Germany
Mailing address:
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Managing Director: Dr. Oliver Baron
Institute for Chemical Epigenetics Munich (ICEM)
Ludwig-Maximilians-Universität München
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81377 Munich Germany
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
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Germany
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Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
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Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
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Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
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