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The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S
- Source :
- Cellular and molecular life sciences (Print. ed.) 75 (2018): 3441–3456. doi:10.1007/s00018-018-2807-y, info:cnr-pdr/source/autori:Sbardella, Diego; Tundo, Grazia R.; Coletta, Andrea; Marcoux, Julien; Koufogeorgou, Efthymia Ioanna; Ciaccio, Chiara; Santoro, Anna M.; Milardi, Danilo; Grasso, Giuseppe; Cozza, Paola; Bousquet-Dubouch, Marie-Pierre; Marini, Stefano; Coletta, Massimo/titolo:The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S/doi:10.1007%2Fs00018-018-2807-y/rivista:Cellular and molecular life sciences (Print. ed.)/anno:2018/pagina_da:3441/pagina_a:3456/intervallo_pagine:3441–3456/volume:75, Cellular and Molecular Life Sciences, Cellular and Molecular Life Sciences, Springer Verlag, 2018, 75 (18), pp.3441-3456. ⟨10.1007/s00018-018-2807-y⟩, Sbardella, D, Tundo, G R, Coletta, A, Marcoux, J, Koufogeorgou, E I, Ciaccio, C, Santoro, A M, Milardi, D, Grasso, G, Cozza, P, Bousquet-Dubouch, M P, Marini, S & Coletta, M 2018, ' The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S ', Cellular and Molecular Life Sciences, vol. 75, no. 18, pp. 3441-3456 . https://doi.org/10.1007/s00018-018-2807-y
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE) 30 nM and activating at (IDE) 30 nM. Only an activating effect is observed in a yeast mutant locked in the "open" conformation (i.e., the alpha-3 Delta N 20S), envisaging a possible role of IDE as modulator of the 20S "open"-"closed" allosteric equilibrium. Protein-protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S alpha-3 subunit which regulates the gate opening of the 20S.
- Subjects :
- 0301 basic medicine
Mutant
Open-close 20S equilibrium
Insulysin
0302 clinical medicine
Tandem Mass Spectrometry
Yeasts
Insulin-degrading enzyme
IDE-20S molecular docking
Chromatography, High Pressure Liquid
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
Chromatography
Tumor
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Molecular Docking Simulation
Native Polyacrylamide Gel Electrophoresis
IDE-20S proteasome interaction
Allosteric Regulation
Cell Line, Tumor
HEK293 Cells
Humans
Kinetics
Proteasome Endopeptidase Complex
Protein Binding
Protein Structure, Quaternary
Protein Structure, Tertiary
Biochemistry
High Pressure Liquid
Molecular Medicine
Protein Structure
Allosteric modulator
Protein subunit
Allosteric regulation
Insulin-degrading enzyme, IDE-20S proteasome interaction, IDE-20S molecular docking, Open-close 20S equilibrium
Cell Line
Quaternary
03 medical and health sciences
Cellular and Molecular Neuroscience
Settore BIO/10
Molecular Biology
Pharmacology
Cell Biology
030104 developmental biology
Enzyme
chemistry
Proteasome
Docking (molecular)
Tertiary
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14209071 and 1420682X
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences
- Accession number :
- edsair.doi.dedup.....79e7902074b94292689ec25b1734736c
- Full Text :
- https://doi.org/10.1007/s00018-018-2807-y