Evidence map›Paper›PMID 19038267›Full record

ArticleJournal of molecular biology2009

Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies.

Matthew Biancalana, Koki Makabe, Akiko Koide, Shohei Koide

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
10.2field-weighted citation impact, top 1% 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

129 citing papers in PubMed, 366 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Neuroprotective Evaluation ofMolecules (Basel, Switzerland) · 2025
    Article
  13. Formation of a β-Endorphin Corona Mitigates Alzheimer's Amyloidogenesis.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

69 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Matthew BiancalanaDepartment of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
Koki Makabe
Akiko Koide
Shohei Koide
University of Chicago · US

Funding

Chaperone Assisted CrystallographyR01GM072688 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2005 to 2012
$2.7M
Undergraduate Training Program in Chemical & Physical B*T90DK070076 · NIDDK · UNIVERSITY OF CHICAGO · PI KRON, STEPHEN J. · 2006 to 2007
$550k
NCI NIH HHS Y1-CO-1020NIDDK NIH HHS T90 DK070076NIDDK NIH HHS T90-DK070076NIGMS NIH HHS R01 GM072688NIGMS NIH HHS R01-GM72688NIGMS NIH HHS Y1-GM-1104
6 · The paper itself

Abstract

A number of small organic molecules have been developed that bind to amyloid fibrils, a subset of which also inhibit fibrillization. Among these, the benzothiol dye Thioflavin-T (ThT) has been used for decades in the diagnosis of protein-misfolding diseases and in kinetic studies of self-assembly (fibrillization). Despite its importance, efforts to characterize the ThT-binding mechanism at the atomic level have been hampered by the inherent insolubility and heterogeneity of peptide self-assemblies. To overcome these challenges, we have developed a minimalist approach to designing a ThT-binding site in a "peptide self-assembly mimic" (PSAM) scaffold. PSAMs are engineered water-soluble proteins that mimic a segment of beta-rich peptide self-assembly, and they are amenable to standard biophysical techniques and systematic mutagenesis. The PSAM beta-sheet contains rows of repetitive amino acid patterns running perpendicular to the strands (cross-strand ladders) that represent a ubiquitous structural feature of fibril-like surfaces. We successfully designed a ThT-binding site that recapitulates the hallmarks of ThT-fibril interactions by constructing a cross-strand ladder consisting of contiguous tyrosines. The X-ray crystal structures suggest that ThT interacts with the beta-sheet by docking onto surfaces formed by a single tyrosine ladder, rather than in the space between adjacent ladders. Systematic mutagenesis further demonstrated that tyrosine surfaces across four or more beta-strands formed the minimal binding site for ThT. Our work thus provides structural insights into how this widely used dye recognizes a prominent subset of peptide self-assemblies, and proposes a strategy to elucidate the mechanisms of fibril-ligand interactions.

Indexed as

BenzothiazolesBinding SitesCrystallography, X-RayModels, BiologicalModels, MolecularPeptidesProtein Structure, SecondarySurface PropertiesThiazolesTyrosineBenzothiazolesPeptidesThiazolesthioflavin TTyrosine

Identifiers

PMID19038267
PMCPMC2664162
OpenAlexW2038399240

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.