UBIQUITINATION-INDUCED CONFORMATIONAL CHANGE WITHIN THE DEIODINASE DIMER IS A SWITCH REGULATING ENZYME ACTIVITY
| Autor: | D. Vivek Sagar, G., Gereben, Balázs, Callebaut, Isabelle, Mornon, Jean-Paul, Zeöld, Anikó, S. da Silva, Wagner, Luongo, Cristina, Dentice, Monica, M. Tente, Susana, Beatriz, C., Freitas, G., W. Harney, John, Marie Zavacki, Ann, C. Bianco, Antonio |
|---|---|
| Přispěvatelé: | Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Harvard Medical School [Boston] (HMS), Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sagar, G. D. V., Gereben, B., Callebaut, I., Mornon, J. -P., Zeold, A., Da Silva, W. S., Luongo, C., Dentice, M., Tente, S. M., Freitas, B. C. G., Harney, J. W., Zavacki, A. M., Bianco, A. C. |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Conformational change Molecular Sequence Data 030209 endocrinology & metabolism Ubiquitin-conjugating enzyme Iodide Peroxidase Catalysis Protein Structure Secondary Catalysi Cell Line Deubiquitinating enzyme Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Ubiquitin Catalytic Domain Animals Humans Amino Acid Sequence Enzyme Reactivation Protein Structure Quaternary Molecular Biology 030304 developmental biology 0303 health sciences biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Animal Articles Cell Biology Transmembrane protein Protein Structure Tertiary Cell biology Ubiquitin ligase Holoenzyme Biochemistry biology.protein Holoenzymes Dimerization Human Protein Binding Deubiquitination |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, 2007, 13, pp.4774-83. ⟨10.1128/MCB.00283-07⟩ Molecular Biology of the Cell, American Society for Cell Biology, 2007, 13, pp.4774-83. ⟨10.1128/MCB.00283-07⟩ |
| ISSN: | 1939-4586 |
| DOI: | 10.1128/MCB.00283-07⟩ |
| Popis: | International audience; Ubiquitination is a critical posttranslational regulator of protein stability and/or subcellular localization. Here we show that ubiquitination can also regulate proteins by transiently inactivating enzymatic function through conformational change in a dimeric enzyme, which can be reversed upon de-ubiquitination. Our model system is the thyroid hormone activating type 2 deiodinase (D2), an endoplasmic reticulum resident type 1 integral membrane enzyme. D2 exists as a homodimer maintained by interacting surfaces at its transmembrane and globular cytosolic domains. The D2 dimer associates with the Hedgehog-inducible ubiquitin ligase WSB-1, the ubiquitin conjugase UBC-7, and VDU-1, a D2-specific deubiquitinase. Upon binding of T4, its natural substrate, D2 is ubiquitinated, which inactivates the enzyme by interfering with D2's globular interacting surfaces that are critical for dimerization and catalytic activity. This state of transient inactivity and change in dimer conformation persists until de-ubiquitination. The continuous association of D2 with this regulatory protein complex supports rapid cycles of deiodination, conjugation to ubiquitin, and enzyme reactivation by de-ubiquitination, allowing tight control of thyroid hormone action. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|