ArticleBiochemistry2018
Analysis of the Role of the Conserved Disulfide in Amyloid Formation by Human Islet Amyloid Polypeptide in Homogeneous and Heterogeneous Environments.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- Impact of Stabilizing Osmolytes on the Conformational Dynamics of Human and Rat Islet Amyloid Polypeptides.Proteins · 2026Article
- Article
- Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.Biophysical chemistry · 2024Review
- Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.Journal of the American Chemical Society · 2024Article
- Improving cryo-EM grids for amyloid fibrils using interface-active solutions and spectator proteins.Biophysical journal · 2024Article
- Article
- 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
- Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2022Review
- The Introduction of a Cysteine Residue Modulates The Mechanical Properties of Aromatic-Based Solid Aggregates and Self-Supporting Hydrogels.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- Fibrillation of Human Calcitonin and Its Analogs: Effects of Phosphorylation and Disulfide Reduction.Biophysical journal · 2021Article
- Amyloid formation of fish β-parvalbumin involves primary nucleation triggered by disulfide-bridged protein dimers.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins.International journal of molecular sciences · 2020Review
- Analysis of Baboon IAPP Provides Insight into Amyloidogenicity and Cytotoxicity of Human IAPP.Biophysical journal · 2020Article
- Amyloidogenicity and cytotoxicity of des-Lys-1 human amylin provides insight into amylin self-assembly and highlights the difficulties of defining amyloidogenicity.Protein engineering, design & selection : PEDS · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Human islet amyloid polypeptide (hIAPP) is a hormone secreted from β-cells in the Islets of Langerhans in response to the same stimuli that lead to insulin secretion. hIAPP plays an adaptive role in glucose homeostasis but misfolds to form insoluble, fibrillar aggregates in type II diabetes that are associated with the disease. Along the misfolding pathway, hIAPP forms species that are toxic to β-cells, resulting in reduced β-cell mass. hIAPP contains a strictly conserved disulfide bond between residues 2 and 7, which forms a small loop at the N-terminus of the molecule. The loop is located outside of the cross β-core in all models of the hIAPP amyloid fibrils. Mutations in this region are rare, and the disulfide loop plays a role in receptor binding; however, the contribution of this region to the aggregation of hIAPP is not well understood. We define the role of the disulfide by analyzing a collection of analogues that remove the disulfide, by mutation of Cys to Ser, by reduction and modification of the Cys residues, or by deletion of the first seven residues. The cytotoxic properties of hIAPP are retained in the Cys to Ser disulfide-free mutant. Removal of the disulfide bond accelerates amyloid formation in all constructs, both in solution and in the presence of model membranes. Removal of the disulfide weakens the ability of hIAPP to induce leakage of vesicles consisting of POPS and POPC. Smaller effects are observed with vesicles that contain 40 mol % cholesterol, although N-terminal truncation still reduces the extent of leakage.
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.