ArticleeLife2017
Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed, 100 citations in OpenAlex.
- Massively parallel quantification of mutational impact on IAPP amyloid formation.Nature communications · 2026Article
- Experimental and computational analysis of the basis for accelerated amyloid formation by a disease linked mutant of human islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2025Article
- Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.Biophysical chemistry · 2024Review
- Computational Investigation of Coaggregation and Cross-Seeding between Aβ and hIAPP Underpinning the Cross-Talk in Alzheimer's Disease and Type 2 Diabetes.Journal of chemical information and modeling · 2024Article
- Fragment-BasedACS bio & med chem Au · 2023Article
- The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study.Heliyon · 2023Article
- Catechol-containing compounds are a broad class of protein aggregation inhibitors: Redox state is a key determinant of the inhibitory activities.Pharmacological research · 2022Article
- Mechanistic insight into functionally different human islet polypeptide (hIAPP) amyloid: the intrinsic role of the C-terminal structural motifs.Physical chemistry chemical physics : PCCP · 2022Article
- Molecular insights into the oligomerization dynamics and conformations of amyloidogenic and non-amyloidogenic amylin from discrete molecular dynamics simulations.Physical chemistry chemical physics : PCCP · 2022Article
- Electron Diffraction of 3D Molecular Crystals.Chemical reviews · 2022Review
- Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective.Bioscience reports · 2022Review
- Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2022Review
- Studying membrane proteins with MicroED.Biochemical Society transactions · 2022Article
- General Principles Underpinning Amyloid Structure.Frontiers in neuroscience · 2022Review
- Understanding and controlling amyloid aggregation with chirality.Current opinion in chemical biology · 2021Review
- Cryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores.Nature structural & molecular biology · 2021Article
- Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.ACS pharmacology & translational science · 2021Article
- Identification of transmissible proteotoxic oligomer-like fibrils that expand conformational diversity of amyloid assemblies.Communications biology · 2021Article
- MicroED in natural product and small molecule research.Natural product reports · 2021Review
- Direct Observation of β-Barrel Intermediates in the Self-Assembly of Toxic SOD1Journal of chemical information and modeling · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP.
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.