The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S
- 28 March 2018
- journal article
- research article
- Published by Springer Nature in Cellular and Molecular Life Sciences
- Vol. 75 (18) , 3441-3456
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 α-3ΔN 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 α-3 subunit which regulates the gate opening of the 20S.Keywords
This publication has 67 references indexed in Scilit:
- Proteolytically Inactive Insulin-Degrading Enzyme Inhibits Amyloid Formation Yielding Non-Neurotoxic Aβ Peptide AggregatesPLOS ONE, 2013
- Molecular architecture of the 26S proteasome holocomplex determined by an integrative approachProceedings of the National Academy of Sciences, 2012
- Complete subunit architecture of the proteasome regulatory particleNature, 2012
- HSP70 mediates dissociation and reassociation of the 26S proteasome during adaptation to oxidative stressFree Radical Biology and Medicine, 2011
- Insulin-degrading Enzyme Modulates the Natriuretic Peptide-mediated Signaling ResponseJournal of Biological Chemistry, 2011
- Proteasome ActivatorsMolecular Cell, 2011
- Recognition and Processing of Ubiquitin-Protein Conjugates by the ProteasomeAnnual Review of Biochemistry, 2009
- Affinity Purification Strategy to Capture Human Endogenous Proteasome Complexes Diversity and to Identify Proteasome-interacting ProteinsMolecular & Cellular Proteomics, 2009
- Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanismNature, 2006
- Comparative Protein Modelling by Satisfaction of Spatial RestraintsJournal of Molecular Biology, 1993