Evidence map›Paper›PMID 19824733›Full record

ArticleJournal of the American Chemical Society2009

K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis.

Mirela Mustata, Ricardo Capone, Hyunbum Jang, Fernando Teran Arce, Srinivasan Ramachandran, Ratnesh Lal, Ruth Nussinov

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Gels of Amyloid Fibers.Biomolecules · 2019
    Article
  8. Structural Analysis of a Trimer of βBiophysical journal · 2019
    Article
  9. Review
  10. Article
  11. 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 · 2016
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Mirela MustataCenter for Nanomedicine and Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Ricardo Capone
Hyunbum Jang
Fernando Teran Arce
Srinivasan Ramachandran
Ratnesh Lal
Ruth Nussinov
Center for Cancer Research · USTel Aviv University · ILUniversity of Chicago · US

Funding

Protein Structure, Stability, and Amyloid FormationZIABC010440 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSINOV, RUTH · 2009 to 2025
$11.8M
Protein Structure, Stability, and Amyloid FormationZ01BC010440 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSINOV, RUTH · 2002 to 2008
$1.4M
Intramural NIH HHS Z01 BC010440NCI NIH HHS N01 CO012400NCI NIH HHS N01-CO-12400
6 · The paper itself

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.

Indexed as

AmyloidAmyloidosisbeta 2-MicroglobulinBiological TransportCalciumCells, CulturedElectric ConductivityHumansIon ChannelsKidneyLipid BilayersMicroscopy, Atomic ForceMolecular Dynamics SimulationPeptide FragmentsRenal DialysisAmyloidbeta 2-MicroglobulinCalciumIon ChannelsLipid BilayersPeptide Fragments

Identifiers

PMID19824733
PMCPMC2782653
OpenAlexW1999007957

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Registered trials

None linked

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.