ArticleThe Journal of biological chemistry2013
Structure, folding dynamics, and amyloidogenesis of D76N β2-microglobulin: roles of shear flow, hydrophobic surfaces, and α-crystallin.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 90 citations in OpenAlex.
- Initiation of transthyretin aggregation at neutral pH by fluid agitation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human wild-type and D76N βFASEB bioAdvances · 2023Article
- Extracellular protein homeostasis in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Disease-relevant βNature communications · 2023Article
- Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis.Nature communications · 2022Article
- The residues 4 to 6 at the N-terminus in particular modulate fibril propagation of β-microglobulin.Acta biochimica et biophysica Sinica · 2022Article
- Amyloid Formation by Globular Proteins: The Need to Narrow the Gap BetweenFrontiers in molecular biosciences · 2022Review
- Pathogenic D76N Variant of βBiology · 2021Article
- Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence.The Journal of pathology · 2021Article
- Global Proteotoxicity Caused by Human βInternational journal of molecular sciences · 2021Article
- Investigation of D76N βJournal of the American Society for Mass Spectrometry · 2021Article
- Predicting stable binding modes from simulated dimers of the D76N mutant ofComputational and structural biotechnology journal · 2021Article
- Insights into a Protein-Nanoparticle System by Paramagnetic Perturbation NMR Spectroscopy.Molecules (Basel, Switzerland) · 2020Article
- Conformational Stability and Dynamics in Crystals Recapitulate Protein Behavior in Solution.Biophysical journal · 2020Article
- The role of the IThe Journal of biological chemistry · 2020Article
- Collagen I Weakly Interacts with the β-Sheets of βJournal of the American Chemical Society · 2020Article
- The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.Frontiers in molecular biosciences · 2020Review
- C. elegans expressing D76N βScientific reports · 2019Article
- Oleuropein, a Bioactive Compound fromAntioxidants (Basel, Switzerland) · 2019Review
- Loosening of Side-Chain Packing Associated with Perturbations in Peripheral Dynamics Induced by the D76N Mutation of βBiomolecules · 2019Article
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin (β2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition.
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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.