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Ubiquitylation Directly Induces Fold Destabilization of Proteins
- Source :
- Scientific Reports
- Publication Year :
- 2016
-
Abstract
- Ubiquitin is a common post-translational modifier and its conjugation is a key signal for proteolysis by the proteasome. Because the molecular mass of ubiquitin is larger than that of other modifiers such as phosphate, acetyl, or methyl groups, ubiquitylation not only influences biochemical signaling, but also may exert physical effects on its substrate proteins by increasing molecular volume and altering shape anisotropy. Here we show that ubiquitylation destabilizes the fold of two proteins, FKBP12 and FABP4, and that elongation of the conjugated ubiquitin chains further enhances this destabilization effect. Moreover, NMR relaxation analysis shows that ubiquitylation induces characteristic structural fluctuations in the backbone of both proteins. These results suggest that the ubiquitylation-driven structural fluctuations lead to fold destabilization of its substrate proteins. Thus, physical destabilization by ubiquitylation may facilitate protein degradation by the proteasome.
- Subjects :
- 0301 basic medicine
Proteomics
Proteasome Endopeptidase Complex
Protein Folding
Magnetic Resonance Spectroscopy
Proteolysis
Plasma protein binding
Tacrolimus Binding Protein 1A
Protein degradation
Fatty Acid-Binding Proteins
Article
03 medical and health sciences
Ubiquitin
medicine
Humans
Multidisciplinary
030102 biochemistry & molecular biology
biology
medicine.diagnostic_test
Calorimetry, Differential Scanning
Chemistry
Temperature
Ubiquitination
030104 developmental biology
FKBP
Spectrometry, Fluorescence
Proteasome
biology.protein
Biophysics
Anisotropy
Protein folding
Signal transduction
Protein Processing, Post-Translational
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....214a6d7cb524e26b81871c17d82a5cbb