ArticleeLife2018
Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 148 citations in OpenAlex.
- Article
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity.bioRxiv : the preprint server for biology · 2025Article
- Disulfide-constrained Fabs overcome target size limitation for high-resolution single particle cryoEM.Nature communications · 2025Article
- Dimerization and dynamics of human angiotensin-I converting enzyme revealed by cryo-EM and MD simulations.eLife · 2025Article
- Understanding the Insulin-Degrading Enzyme: A New Look at Alzheimer's Disease and Aβ Plaque Management.International journal of molecular sciences · 2025Review
- Highly toxic Aβ begets more Aβ.Neural regeneration research · 2024Article
- Diselenide-bond replacement of the external disulfide bond of insulin increases its oligomerization leading to sustained activity.Communications chemistry · 2023Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Conformation-specific Synthetic Antibodies Discriminate Multiple Functional States of the Ion Channel CorA.Journal of molecular biology · 2023Article
- Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid β Oligomers by Insulin Degrading Enzyme.Biomolecules · 2022Article
- Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes.ACS omega · 2022Article
- Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.Nature communications · 2022Article
- Review
- Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
- Article
- Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme.Antioxidants (Basel, Switzerland) · 2021Article
- Generation and characterization of a laforin nanobody inhibitor.Clinical biochemistry · 2021Article
- Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states.Structure (London, England : 1993) · 2021Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
Abstract
Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.