ArticleJournal of molecular biology2017
Molecular Origins of the Compatibility between Glycosaminoglycans and Aβ40 Amyloid Fibrils.
Article in Journal of molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Serum Amyloid A Binding to Glycosaminoglycans is Synergistic with Amyloid Formation: Therapeutic Targeting in the Inflammation-linked Amyloidosis.Journal of molecular biology · 2025Article
- Aging and Alzheimer's: the critical role of mitochondrial dysfunction and synaptic alterations.Frontiers in synaptic neuroscience · 2025Review
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Amyloid seeding as a disease mechanism and treatment target in transthyretin cardiac amyloidosis.Heart failure reviews · 2022Review
- Protein Amyloid Cofactors: Charged Side-Chain Arrays Meet Their Match?Trends in biochemical sciences · 2021Article
- Glycosaminoglycans in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2021Review
- Aggregation Kinetics and Filament Structure of a Tau Fragment Are Influenced by the Sulfation Pattern of the Cofactor Heparin.Biochemistry · 2020Article
- Amyloid structures: much more than just a cross-β fold.Current opinion in structural biology · 2020Review
- Extracellular matrix components modulate different stages in βThe Journal of biological chemistry · 2019Article
- Molecular insights into the surface-catalyzed secondary nucleation of amyloid-βScience advances · 2019Article
- Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies.Molecular cell · 2019Article
- A Glycosaminoglycan Extract fromMarine drugs · 2019Article
- Zinc binding regulates amyloid-like aggregation of GAPR-1.Bioscience reports · 2019Article
- A new era for understanding amyloid structures and disease.Nature reviews. Molecular cell biology · 2018Review
- Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy.Molecules (Basel, Switzerland) · 2018Review
- Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin.The Journal of biological chemistry · 2018Article
- The Early Events That Initiate β-Amyloid Aggregation in Alzheimer's Disease.Frontiers in aging neuroscience · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The Aβ peptide forms extracellular plaques associated with Alzheimer's disease. In addition to protein fibrils, amyloid plaques also contain non-proteinaceous components, including glycosaminoglycans (GAGs). We have shown previously that the GAG low-molecular-weight heparin (LMWH) binds to Aβ40 fibrils with a three-fold-symmetric (3Q) morphology with higher affinity than Aβ40 fibrils in alternative structures, Aβ42 fibrils, or amyloid fibrils formed from other sequences. Solid-state NMR analysis of the GAG-3Q fibril complex revealed an interaction site at the corners of the 3Q fibril structure, but the origin of the binding specificity remained obscure. Here, using a library of short heparin polysaccharides modified at specific sites, we show that the N-sulfate or 6-O-sulfate of glucosamine, but not the 2-O-sulfate of iduronate within heparin is required for 3Q binding, indicating selectivity in the interactions of the GAG with the fibril that extends beyond general electrostatic complementarity. By creating 3Q fibrils containing point substitutions in the amino acid sequence, we also show that charged residues at the fibril three-fold apices provide the majority of the binding free energy, while charged residues elsewhere are less critical for binding. The results indicate, therefore, that LMWH binding to 3Q fibrils requires a precise molecular complementarity of the sulfate moieties on the GAG and charged residues displayed on the fibril surface. Differences in GAG binding to fibrils with distinct sequence and/or structure may thus contribute to the diverse etiology and progression of amyloid diseases.
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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.