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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zobel, Kerry Deshayes, Kurt Wallweber, Heidi J. A. Vucic, Domagoj Fairbrother, Wayne J. Hymowitz, Sarah G. Dueber, Erin C. Lingel, Andreas Maurer, Brigitte Giannetti, Anthony M. Elliott, J. Michael Fedorova, Anna V. Schoeffler, Allyn J. Wu, Ping Varfolomeev, Eugene |
| Description | Author Affiliation: Dueber EC ( Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.) |
| Abstract | Inhibitor of apoptosis (IAP) proteins are negative regulators of cell death. IAP family members contain RING domains that impart E3 ubiquitin ligase activity. Binding of endogenous or small-molecule antagonists to select baculovirus IAP repeat (BIR) domains within cellular IAP (cIAP) proteins promotes autoubiquitination and proteasomal degradation and so releases inhibition of apoptosis mediated by cIAP. Although the molecular details of antagonist-BIR domain interactions are well understood, it is not clear how this binding event influences the activity of the RING domain. Here biochemical and structural studies reveal that the unliganded, multidomain cIAP1 sequesters the RING domain within a compact, monomeric structure that prevents RING dimerization. Antagonist binding induces conformational rearrangements that enable RING dimerization and formation of the active E3 ligase. |
| ISSN | 00368075 |
| Issue Number | 6054 |
| Volume Number | 334 |
| e-ISSN | 10959203 |
| Journal | Science |
| Language | English |
| Publisher | American Association for the Advancement of Science (United States) |
| Publisher Date | 2011-10-21 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Inhibitor Of Apoptosis Proteins Antagonists & Inhibitors Chemistry Amino Acid Sequence Animals Cell Line Cell Line, Tumor Cloning, Molecular Humans Hydrophobic And Hydrophilic Interactions Metabolism Mice Models, Biological Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Proteasome Endopeptidase Complex Protein Conformation Protein Interaction Domains And Motifs Protein Multimerization Protein Structure, Secondary Scattering, Small Angle Ubiquitin-Protein Ligases Ubiquitinated Proteins Ubiquitination Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | History and Philosophy of Science |
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