ArticleBiophysical journal2014
Mutational analysis of preamyloid intermediates: the role of his-tyr interactions in islet amyloid formation.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 33 citations in OpenAlex.
- Mammals that can develop type 2 diabetes have a similarly structured β-sheet amyloid oligomer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms.Molecular metabolism · 2025Article
- Zinc and pH modulate the ability of insulin to inhibit aggregation of islet amyloid polypeptide.Communications biology · 2024Article
- Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid-Liquid Interfaces.International journal of molecular sciences · 2021Article
- Low concentration IL-1β promotes islet amyloid formation by increasing hIAPP release from humanised mouse islets in vitro.Diabetologia · 2020Article
- PAM haploinsufficiency does not accelerate the development of diet- and human IAPP-induced diabetes in mice.Diabetologia · 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
- Protein Glycation by Glyoxal Promotes Amyloid Formation by Islet Amyloid Polypeptide.Biophysical journal · 2019Article
- Molecular Signature for Receptor Engagement in the Metabolic Peptide Hormone Amylin.ACS pharmacology & translational science · 2018Article
- Site-specific detection of protein secondary structure using 2D IR dihedral indexing: a proposed assembly mechanism of oligomeric hIAPP.Chemical science · 2018Article
- Understanding co-polymerization in amyloid formation by direct observation of mixed oligomers.Chemical science · 2017Article
- Effect of Post-Translational Amidation on Islet Amyloid Polypeptide Conformational Ensemble: Implications for Its Aggregation Early Steps.International journal of molecular sciences · 2016Article
- Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology.Journal of diabetes research · 2016Review
- Article
- Insights into the consequences of co-polymerisation in the early stages of IAPP and Aβ peptide assembly from mass spectrometry.The Analyst · 2015Article
- Probing the sources of the apparent irreproducibility of amyloid formation: drastic changes in kinetics and a switch in mechanism due to micellelike oligomer formation at critical concentrations of IAPP.The journal of physical chemistry. B · 2015Article
- Article
- Rationally designed, nontoxic, nonamyloidogenic analogues of human islet amyloid polypeptide with improved solubility.Biochemistry · 2014Article
- Amyloid fibrils: the eighth wonder of the world in protein folding and aggregation.Biophysical journal · 2014Article
Corrections and comments
- Commented on by
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Islet amyloid polypeptide (IAPP or Amylin) is a 37-residue, C-terminally amidated pancreatic hormone, cosecreted with insulin that forms islet amyloid in type 2 diabetes. Islet amyloid formation is complex and characterizing preamyloid oligomers is an important topic because oligomeric intermediates are postulated to be the most toxic species produced during fibril formation. A range of competing models for early oligomers have been proposed. The role of the amidated C-terminus in amyloid formation by IAPP and in stabilizing oligomers is not known. Studies with unamidated IAPP have provided evidence for formation of an antiparallel dimer at pH 5.5, stabilized by stacking of His-18 and Tyr-37, but it is not known if this interaction is formed in the physiological form of the peptide. Analysis of a set of variants with a free and with an amidated C-terminus shows that disrupting the putative His-Tyr interaction accelerates amyloid formation, indicating that it is not essential. Amidation to generate the physiologically relevant form of IAPP accelerates amyloid formation, demonstrating that the advantages conferred by C-terminal amidation outweigh increased amyloidogenicity. The analysis of this variant argues that IAPP is not under strong evolutionary pressure to reduce amyloidogenicity. Analysis of an H18Q mutant of IAPP shows that the charge state of the N-terminus is an important factor controlling the rate of amyloid formation, even though the N-terminal region of IAPP is believed to be flexible in the amyloid fibers.
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.