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22 results on '"Sherpa, Dawafuti"'

5. Skraban‐Deardorff intellectual disability syndrome‐associated mutations in WDR26 impair CTLH E3 complex assembly.

Author

Gross, Annette, Müller, Judith, Chrustowicz, Jakub, Strasser, Alexander, Gottemukkala, Karthik V., Sherpa, Dawafuti, Schulman, Brenda A., Murray, Peter J., and Alpi, Arno F.

Subjects
INTELLECTUAL disabilities, ERGONOMICS, STRUCTURAL models, DEVELOPMENTAL delay, UBIQUITIN ligases
Abstract

Patients with Skraban‐Deardorff syndrome (SKDEAS), a neurodevelopmental syndrome associated with a spectrum of developmental and intellectual delays and disabilities, harbor diverse mutations in WDR26, encoding a subunit of the multiprotein CTLH E3 ubiquitin ligase complex. Structural studies revealed that homodimers of WDR26 bridge two core‐CTLH E3 complexes to generate giant, hollow oval‐shaped supramolecular CTLH E3 assemblies. Additionally, WDR26 mediates CTLH E3 complex binding to subunit YPEL5 and functions as substrate receptor for the transcriptional repressor HBP1. Here, we mapped SKDEAS‐associated mutations on a WDR26 structural model and tested their functionality in complementation studies using genetically engineered human cells lacking CTLH E3 supramolecular assemblies. Despite the diversity of mutations, 15 of 16 tested mutants impaired at least one CTLH E3 complex function contributing to complex assembly and interactions, thus providing first mechanistic insights into SKDEAS pathology. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Structural and functional characterization of GID/CTLH E3 ubiquitin ligases

Author

Schulman, Brenda A. (Prof., Ph.D.), Schulman, Brenda A. (Prof., Ph.D.);Sattler, Michael (Prof. Dr.);Finley, Daniel (Prof., Ph.D.), Sherpa, Dawafuti, Schulman, Brenda A. (Prof., Ph.D.), Schulman, Brenda A. (Prof., Ph.D.);Sattler, Michael (Prof. Dr.);Finley, Daniel (Prof., Ph.D.), and Sherpa, Dawafuti

Abstract

We know little about how E3 ubiquitin ligases are configured to match protein features like different folds, oligomeric states and post-translational modifications. By studying GID/CTLH E3, we answer some of these fundamental questions. We have uncovered a higher-order assembly of the GID as a strategy for targeting its oligomeric substrate Fbp1 and elucidated how the pliable nature of the GID substrate receptors allows for a variety of substrate degron binding. Moreover, we show that these structural and biochemical features are conserved in its human ortholog, CTLH complex., Wir wissen wenig darüber, wie E3 Ubiquitin Ligasen konfiguriert sind, um Proteinmerkmale wie diverse Faltungen, oligomere Zustände und posttranslationale Modifikationen anzupassen. Durch die Untersuchung von GID/CTLH E3 können wir dieser Fragen beantworten. Wir haben einen Aufbau höherer Ordnung des GID E3 als Strategie für die Regulierung auf sein oligomeres Substrat Fbp1 endeckt und aufgeklärt, wie die biegsame Natur der GID-Substratrezeptoren eine Vielzahl von Substrat-degron Bindungen ermöglicht. Weiterhin zeigen wir, dass diese Merkmale in seinem menschlichen Ortholog, dem CTLH Komplex, konserviert sind.

Published
2023

7. Modular UBE2H-CTLH E2-E3 complexes regulate erythroid maturation

Author

Sherpa, Dawafuti, primary, Mueller, Judith, primary, Karayel, Özge, primary, Xu, Peng, primary, Yao, Yu, additional, Chrustowicz, Jakub, additional, Gottemukkala, Karthik V, additional, Baumann, Christine, additional, Gross, Annette, additional, Czarnecki, Oliver, additional, Zhang, Wei, additional, Gu, Jun, additional, Nilvebrant, Johan, additional, Sidhu, Sachdev S, additional, Murray, Peter J, additional, Mann, Matthias, additional, Weiss, Mitchell J, additional, Schulman, Brenda A, additional, and Alpi, Arno F, additional

Published
2022
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8. Strukturelle und funktionelle Charakterisierung von GID/CTLH E3-Ligasen

Author

Sherpa, Dawafuti, Schulman, Brenda A. (Prof., Ph.D.), Sattler, Michael (Prof. Dr.), and Finley, Daniel (Prof., Ph.D.)

Subjects
ubiquitin, E3 ligases, protein degradation, GID, CTLH, ddc:540, Chemie
Abstract

We know little about how E3 ubiquitin ligases are configured to match protein features like different folds, oligomeric states and post-translational modifications. By studying GID/CTLH E3, we answer some of these fundamental questions. We have uncovered a higher-order assembly of the GID as a strategy for targeting its oligomeric substrate Fbp1 and elucidated how the pliable nature of the GID substrate receptors allows for a variety of substrate degron binding. Moreover, we show that these structural and biochemical features are conserved in its human ortholog, CTLH complex. Wir wissen wenig darüber, wie E3 Ubiquitin Ligasen konfiguriert sind, um Proteinmerkmale wie diverse Faltungen, oligomere Zustände und posttranslationale Modifikationen anzupassen. Durch die Untersuchung von GID/CTLH E3 können wir dieser Fragen beantworten. Wir haben einen Aufbau höherer Ordnung des GID E3 als Strategie für die Regulierung auf sein oligomeres Substrat Fbp1 endeckt und aufgeklärt, wie die biegsame Natur der GID-Substratrezeptoren eine Vielzahl von Substrat-degron Bindungen ermöglicht. Weiterhin zeigen wir, dass diese Merkmale in seinem menschlichen Ortholog, dem CTLH Komplex, konserviert sind.

Published
2023

9. Author response: Modular UBE2H-CTLH E2-E3 complexes regulate erythroid maturation

Author

Sherpa, Dawafuti, primary, Mueller, Judith, primary, Karayel, Özge, primary, Xu, Peng, primary, Yao, Yu, additional, Chrustowicz, Jakub, additional, Gottemukkala, Karthik V, additional, Baumann, Christine, additional, Gross, Annette, additional, Czarnecki, Oliver, additional, Zhang, Wei, additional, Gu, Jun, additional, Nilvebrant, Johan, additional, Sidhu, Sachdev S, additional, Murray, Peter J, additional, Mann, Matthias, additional, Weiss, Mitchell J, additional, Schulman, Brenda A, additional, and Alpi, Arno F, additional

Published
2022
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10. Modular UBE2H-CTLH E2-E3 complexes regulate erythroid maturation

Author

Sherpa, Dawafuti, Mueller, Judith, Karayel, Oezge, Xu, Peng, Yao, Yu, Chrustowicz, Jakub, Gottemukkala, Karthik, V, Baumann, Christine, Gross, Annette, Czarnecki, Oliver, Zhang, Wei, Gu, Jun, Nilvebrant, Johan, Sidhu, Sachdev S., Murray, Peter J., Mann, Matthias, Weiss, Mitchell J., Schulman, Brenda A., Alpi, Arno F., Sherpa, Dawafuti, Mueller, Judith, Karayel, Oezge, Xu, Peng, Yao, Yu, Chrustowicz, Jakub, Gottemukkala, Karthik, V, Baumann, Christine, Gross, Annette, Czarnecki, Oliver, Zhang, Wei, Gu, Jun, Nilvebrant, Johan, Sidhu, Sachdev S., Murray, Peter J., Mann, Matthias, Weiss, Mitchell J., Schulman, Brenda A., and Alpi, Arno F.

Abstract

The development of haematopoietic stem cells into mature erythrocytes - erythropoiesis - is a controlled process characterized by cellular reorganization and drastic reshaping of the proteome landscape. Failure of ordered erythropoiesis is associated with anaemias and haematological malignancies. Although the ubiquitin system is a known crucial post-translational regulator in erythropoiesis, how the erythrocyte is reshaped by the ubiquitin system is poorly understood. By measuring the proteomic landscape of in vitro human erythropoiesis models, we found dynamic differential expression of subunits of the CTLH E3 ubiquitin ligase complex that formed maturation stage-dependent assemblies of topologically homologous RANBP9- and RANBP10-CTLH complexes. Moreover, protein abundance of CTLH's cognate E2 ubiquitin conjugating enzyme UBE2H increased during terminal differentiation, and UBE2H expression depended on catalytically active CTLH E3 complexes. CRISPR-Cas9-mediated inactivation of CTLH E3 assemblies or UBE2H in erythroid progenitors revealed defects, including spontaneous and accelerated erythroid maturation as well as inefficient enucleation. Thus, we propose that dynamic maturation stage-specific changes of UBE2H-CTLH E2-E3 modules control the orderly progression of human erythropoiesis., QC 20221223

Published
2022
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12. Differential UBE2H-CTLH E2-E3 ubiquitylation modules regulate erythroid maturation

Author

Sherpa, Dawafuti, primary, Müller, Judith, additional, Karayel, Özge, additional, Chrustowicz, Jakub, additional, Xu, Peng, additional, Gottemukkala, Karthik V., additional, Baumann, Christine, additional, Gross, Annette, additional, Czarnezki, Oliver, additional, Zhang, Wei, additional, Gu, Jun, additional, Nilvebrant, Johan, additional, Weiss, Mitchell J., additional, Sidhu, Sachdev S., additional, Murray, Peter J., additional, Mann, Matthias, additional, Schulman, Brenda A., additional, and Alpi, Arno F., additional

Published
2022
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16. GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

Author

Sherpa, Dawafuti, primary, Chrustowicz, Jakub, additional, Qiao, Shuai, additional, Langlois, Christine R., additional, Hehl, Laura A., additional, Gottemukkala, Karthik Varma, additional, Hansen, Fynn M., additional, Karayel, Ozge, additional, von Gronau, Susanne, additional, Prabu, J. Rajan, additional, Mann, Matthias, additional, Alpi, Arno F., additional, and Schulman, Brenda A., additional

Published
2021
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19. Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Author

Qiao, Shuai, primary, Langlois, Christine R., additional, Chrustowicz, Jakub, additional, Sherpa, Dawafuti, additional, Karayel, Ozge, additional, Hansen, Fynn M., additional, Beier, Viola, additional, von Gronau, Susanne, additional, Bollschweiler, Daniel, additional, Schäfer, Tillman, additional, Alpi, Arno F., additional, Mann, Matthias, additional, Prabu, J. Rajan, additional, and Schulman, Brenda A., additional

Published
2020
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20. A low-cost fluorescence reader for in vitro transcription and nucleic acid detection with Cas13a

Author

Katzmeier, Florian, primary, Aufinger, Lukas, additional, Dupin, Aurore, additional, Quintero, Jorge, additional, Lenz, Matthias, additional, Bauer, Ludwig, additional, Klumpe, Sven, additional, Sherpa, Dawafuti, additional, Dürr, Benedikt, additional, Honemann, Maximilian, additional, Styazhkin, Igor, additional, Simmel, Friedrich C., additional, and Heymann, Michael, additional

Published
2019
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22. Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Author

Qiao, Shuai, primary, Langlois, Christine R., additional, Chrustowicz, Jakub, additional, Sherpa, Dawafuti, additional, Karayel, Ozge, additional, Hansen, Fynn M., additional, Beier, Viola, additional, von Gronau, Susanne, additional, Bollschweiler, Daniel, additional, Schäfer, Tillman, additional, Alpi, Arno F., additional, Mann, Matthias, additional, Prabu, J. Rajan, additional, and Schulman, Brenda A., additional

Published
2019
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