ArticleNature communications2018
Conformational switching within dynamic oligomers underpins toxic gain-of-function by diabetes-associated amyloid.
Article in Nature communications, 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Massively parallel quantification of mutational impact on IAPP amyloid formation.Nature communications · 2026Article
- Resveratrol modulates pancreatic proteotoxic stress and metabolic dysfunction in human IAPP transgenic mice.Frontiers in endocrinology · 2026Article
- A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions.ACS chemical neuroscience · 2024Article
- RIPK3 promotes islet amyloid-induced β-cell loss and glucose intolerance in a humanized mouse model of type 2 diabetes.Molecular metabolism · 2024Article
- Dynamic conformational changes of a tardigrade group-3 late embryogenesis abundant protein modulate membrane biophysical properties.PNAS nexus · 2024Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Fluorescence Resonance Energy Transfer to Detect Plasma Membrane Perturbations in Giant Plasma Membrane Vesicles.Bio-protocol · 2023Article
- On-Pathway Oligomer of Human Islet Amyloid Polypeptide Induced and Stabilized by Mechanical Rotation during Magic Angle Spinning Nuclear Magnetic Resonance.The journal of physical chemistry letters · 2023Article
- Unnatural helical peptidic foldamers as protein segment mimics.Chemical Society reviews · 2023Review
- On-Pathway Oligomer of Human Islet Amyloid Polypeptide Induced and Stabilized by Mechanical Rotation During MAS NMR.bioRxiv : the preprint server for biology · 2023Article
- Fibril elongation by human islet amyloid polypeptide is the main event linking aggregation to membrane damage.BBA advances · 2023Article
- Toxic SOD1 trimers are off-pathway in the formation of amyloid-like fibrils in ALS.Biophysical journal · 2022Article
- Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.Nature communications · 2022Article
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- Identification of transmissible proteotoxic oligomer-like fibrils that expand conformational diversity of amyloid assemblies.Communications biology · 2021Article
- FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic β-cells.The Biochemical journal · 2021Article
- Defining the Neuropathological Aggresome acrossThe journal of physical chemistry. B · 2021Review
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- Membrane Interactions and Toxicity by Misfolded Protein Oligomers.Frontiers in cell and developmental biology · 2021Review
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Peptide mediated gain-of-toxic function is central to pathology in Alzheimer's, Parkinson's and diabetes. In each system, self-assembly into oligomers is observed and can also result in poration of artificial membranes. Structural requirements for poration and the relationship of structure to cytotoxicity is unaddressed. Here we focus on islet amyloid polypeptide (IAPP) mediated loss-of-insulin secreting cells in patients with diabetes. Newly developed methods enable structure-function enquiry to focus on intracellular oligomers composed of hundreds of IAPP. The key insights are that porating oligomers are internally dynamic, grow in discrete steps and are not canonical amyloid. Moreover, two classes of poration occur; an IAPP-specific ligand establishes that only one is cytotoxic. Toxic rescue occurs by stabilising non-toxic poration without displacing IAPP from mitochondria. These insights illuminate cytotoxic mechanism in diabetes and also provide a generalisable approach for enquiry applicable to other partially ordered protein assemblies.
Indexed as
Identifiers
What OpenQuestion holds
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.