ArticleJournal of the American Chemical Society2009
K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis.
Article in Journal of the American Chemical Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Review
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (International ed. in English) · 2023Review
- Pore Formation Mechanism of A-Beta Peptide on the Fluid Membrane: A Combined Coarse-Grained and All-Atomic Model.Molecules (Basel, Switzerland) · 2022Article
- General Principles Underpinning Amyloid Structure.Frontiers in neuroscience · 2022Review
- Medin Oligomer Membrane Pore Formation: A Potential Mechanism of Vascular Dysfunction.Biophysical journal · 2020Article
- Examination of Adsorption Orientation of Amyloidogenic Peptides Over Nano-Gold Colloidal Particle Surfaces.International journal of molecular sciences · 2019Article
- Gels of Amyloid Fibers.Biomolecules · 2019Article
- Structural Analysis of a Trimer of βBiophysical journal · 2019Article
- Vibrational Approach to the Dynamics and Structure of Protein Amyloids.Molecules (Basel, Switzerland) · 2019Review
- Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation.International journal of molecular sciences · 2017Article
- The higher level of complexity of K-Ras4B activation at the membrane.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Computational Methods for Structural and Functional Studies of Alzheimer's Amyloid Ion Channels.Methods in molecular biology (Clifton, N.J.) · 2016Article
- X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin.Journal of the American Chemical Society · 2015Article
- Disordered amyloidogenic peptides may insert into the membrane and assemble into common cyclic structural motifs.Chemical Society reviews · 2014Review
- Role of the fast kinetics of pyroglutamate-modified amyloid-β oligomers in membrane binding and membrane permeability.Biochemistry · 2014Article
- Activity and architecture of pyroglutamate-modified amyloid-β (AβpE3-42) pores.The journal of physical chemistry. B · 2014Article
- Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels.Physical chemistry chemical physics : PCCP · 2014Article
- Mechanism of membrane permeation induced by synthetic β-hairpin peptides.Biophysical journal · 2013Article
- Familial Alzheimer's disease Osaka mutant (ΔE22) β-barrels suggest an explanation for the different Aβ1-40/42 preferred conformational states observed by experiment.The journal of physical chemistry. B · 2013Article
- Molecular interactions of Alzheimer amyloid-β oligomers with neutral and negatively charged lipid bilayers.Physical chemistry chemical physics : PCCP · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Beta(2)-microglobulin (beta(2)m) amyloid deposits are linked to dialysis-related amyloidosis (DRA) in hemodialysis patients. The mechanism by which beta(2)m causes DRA is not understood. It is also unclear whether only the full-length beta(2)m induces pathophysiology or if proteolytic fragments are sufficient for inducing this effect. Ser20-Lys41 (K3) is a digestion fragment of full-length beta(2)m. Solid state NMR (ssNMR) combined with X-ray diffraction and atomic force microscopy (AFM) revealed the characteristic oligomeric amyloid conformation of the U-turn beta-strand-turn-beta-strand motif stacked in parallel and stabilized by intermolecular interactions also shown by Abeta(9-40)/Abeta(17-42) and the CA150 WW domain. Here we use the K3 U-turn atomic coordinates and molecular dynamic (MD) simulations to model K3 channels in the membrane. Consistent with previous AFM imaging of other amyloids that show channel-like structures in the membrane, in the simulations K3 also forms ion channels with 3-6 loosely attached mobile subunits. We carry out AFM, single channel electrical recording, and fluorescence imaging experiments. AFM images display 3D ion channel topography with shapes, morphologies, and dimensions consistent with the theoretical model. Electrical conductance measurements indicate multiple single channel conductances, suggesting that various K3 oligomer sizes can constitute the channel structure. Fluorescence measurements in kidney cells show channel-mediated cell calcium uptake. These results suggest that the beta(2)m-induced DRA can be mediated by ion channels formed by its K3 fragment. Because the beta-strand-turn-beta-strand motif appears to be a universal amyloid feature, its ability to form ion channels further suggests that the motif may play a generic role in toxicity.
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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.