Evidence map›Paper›PMID 31350392›Full record

ArticleNature communications2019

Structure of amyloid-β (20-34) with Alzheimer's-associated isomerization at Asp23 reveals a distinct protofilament interface.

Rebeccah A Warmack, David R Boyer, Chih-Te Zee, Logan S Richards, Michael R Sawaya, Duilio Cascio, Tamir Gonen, David S Eisenberg, Steven G Clarke

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
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

35 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Fragment-BasedACS bio & med chem Au · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Molecular Damage in Aging.Nature aging · 2021
    Review
  20. Review
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

9 authors.

Rebeccah A WarmackDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.ORCID http://orcid.org/0000-0002-9612-0511
David R BoyerDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.
Chih-Te ZeeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.
Logan S RichardsDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.
Michael R SawayaDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.ORCID http://orcid.org/0000-0003-0874-9043
Duilio CascioDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.ORCID http://orcid.org/0000-0001-8285-754X
Tamir GonenMolecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095-1570, USA.ORCID http://orcid.org/0000-0002-9254-4069
David S EisenbergDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA.ORCID http://orcid.org/0000-0003-2432-5419
Steven G ClarkeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095-1569, USA. clarke@mbi.ucla.edu.

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Structure and Inhibition of Amyloid in Alzheimer's DiseaseRF1AG054022 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EISENBERG, DAVID · 2016 to 2018
$4.2M
Micro Electron Diffraction of Toxic and/or Infectious Macromolecular NanoassembliesR35GM128867 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jose Alfonso Rodriguez · 2018 to 2026
$3.1M
West/Midwest Consortium for High-Resolution Cryo Electron MicroscopyU24GM116792 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGBANDJE-MCKENNA, MAVIS, DOKLAND, TERJE · 2016 to 2020
$3.0M
HIGH-END CRYOEM INSTRUMENT FOR UCLA ELECTRON IMAGING CTR FOR NANOMACHINES: AIDSS10RR023057 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHOU, Z HONG · 2006 to 2006
$1.6M
Quantitative Mass Spectrometer for Targeted and Global Proteomics, MetabolomicsS10OD016387 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRAEBER, THOMAS G · 2013 to 2013
$593k
NCRR NIH HHS S10 RR023057NIA NIH HHS RF1 AG054022NIGMS NIH HHS R35 GM128867NIGMS NIH HHS T32 GM007185NIGMS NIH HHS U24 GM116792NIH HHS S10 OD016387
6 · The paper itself

Abstract

Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20-34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20-34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD.

Indexed as

Alzheimer DiseaseAmino Acid SequenceAmyloid beta-PeptidesAspartic AcidHumansIsoaspartic AcidIsomerismMutationProtein ConformationAmyloid beta-PeptidesAspartic AcidIsoaspartic Acid

Identifiers

PMID31350392
PMCPMC6659688

What OpenQuestion holds

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Registered trials

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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.