ArticlePLoS computational biology2014
A simulated intermediate state for folding and aggregation provides insights into ΔN6 β2-microglobulin amyloidogenic behavior.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- CRISPR-AuNP: physicochemical optimization of a gold nanoparticle platform for cost-effective and modular non-viral gene editing in HSPCs.Gene therapy · 2026Article
- β2M Signals Monocytes Through Non-Canonical TGFβ Receptor Signal Transduction.Circulation research · 2021Article
- Predicting stable binding modes from simulated dimers of the D76N mutant ofComputational and structural biotechnology journal · 2021Article
- The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.Frontiers in molecular biosciences · 2020Review
- The Early Phase of β2m Aggregation: An Integrative Computational Study Framed on the D76N Mutant and the ΔN6 Variant.Biomolecules · 2019Article
- Anti-Correlation between the Dynamics of the Active Site Loop and C-Terminal Tail in Relation to the Homodimer Asymmetry of the Mouse Erythroid 5-Aminolevulinate Synthase.International journal of molecular sciences · 2018Article
- Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-likeInternational journal of molecular sciences · 2018Article
- Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation.International journal of molecular sciences · 2017Article
- The Conformation of Interfacially Adsorbed Ranaspumin-2 Is an Arrested State on the Unfolding Pathway.Biophysical journal · 2016Article
- Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.PLoS computational biology · 2016Article
- Uncovering the Early Assembly Mechanism for Amyloidogenic β2-Microglobulin Using Cross-linking and Native Mass Spectrometry.The Journal of biological chemistry · 2016Article
- A covalent homodimer probing early oligomers along amyloid aggregation.Scientific reports · 2015Article
- Exploring the balance between folding and functional dynamics in proteins and RNA.International journal of molecular sciences · 2015Article
- Knotted proteins: A tangled tale of Structural Biology.Computational and structural biotechnology journal · 2015Review
- Intermediates in the folding equilibrium of repeat proteins from the TPR family.European biophysics journal : EBJ · 2014Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
A major component of ex vivo amyloid plaques of patients with dialysis-related amyloidosis (DRA) is a cleaved variant of β2-microglobulin (ΔN6) lacking the first six N-terminal residues. Here we perform a computational study on ΔN6, which provides clues to understand the amyloidogenicity of the full-length β2-microglobulin. Contrary to the wild-type form, ΔN6 is able to efficiently nucleate fibrillogenesis in vitro at physiological pH. This behavior is enhanced by a mild acidification of the medium such as that occurring in the synovial fluid of DRA patients. Results reported in this work, based on molecular simulations, indicate that deletion of the N-terminal hexapeptide triggers the formation of an intermediate state for folding and aggregation with an unstructured strand A and a native-like core. Strand A plays a pivotal role in aggregation by acting as a sticky hook in dimer assembly. This study further predicts that the detachment of strand A from the core is maximized at pH 6.2 resulting into higher aggregation efficiency. The structural mapping of the dimerization interface suggests that Tyr10, His13, Phe30 and His84 are hot-spot residues in ΔN6 amyloidogenesis.
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