Evidence map›Paper›PMID 29681525›Full record

ArticleCell chemical biology2018

Site-Specific Three-Color Labeling of α-Synuclein via Conjugation to Uniquely Reactive Cysteines during Assembly by Native Chemical Ligation.

Taehyung C Lee, Crystal R Moran, Philip A Cistrone, Philip E Dawson, Ashok A Deniz

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  7. Monitoring α-synuclein aggregation.Neurobiology of disease · 2023
    Review
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  9. Article
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  11. Article
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  14. Novel protein science enabled by total chemical synthesis.Protein science : a publication of the Protein Society · 2019
    Review
  15. Article
  16. 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

5 authors at 1 institution in 1 country.

Taehyung C LeeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Crystal R MoranDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: crystal.r.moran@gmail.com.
Philip A CistroneDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Philip E DawsonDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: dawson@scripps.edu.
Ashok A DenizDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: deniz@scripps.edu.
Scripps Research Institute · US

Funding

Single Molecule Studies of Protein Folding MechanismsR01GM066833 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DENIZ, ASHOK A · 2003 to 2017
$5.2M
Glycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8M
Cyclic EphA4 peptide antagonists for neuroprotection in ALSR01NS087070 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PASQUALE, ELENA B · 2014 to 2018
$3.5M
NIAID NIH HHS R01 AI113867NIGMS NIH HHS R01 GM066833NINDS NIH HHS R01 NS087070
6 · The paper itself

Abstract

Single-molecule fluorescence is widely used to study conformational complexity in proteins, and has proven especially valuable with intrinsically disordered proteins (IDPs). Protein studies using dual-color single-molecule Förster resonance energy transfer (smFRET) are now quite common, but many could benefit from simultaneous measurement of multiple distances through multi-color labeling. Such studies, however, have suffered from limitations in site-specific incorporation of more than two dyes per polypeptide. Here we present a fully site-specific three-color labeling scheme for α-synuclein, an IDP with important putative functions and links to Parkinson disease. The convergent synthesis combines native chemical ligation with regiospecific cysteine protection of expressed protein fragments to permit highly controlled labeling via standard cysteine-maleimide chemistry, enabling more global smFRET studies. Furthermore, this modular approach is generally compatible with recombinant proteins and expandable to accommodate even more complex experiments, such as by labeling with additional colors.

Indexed as

Coloralpha-SynucleinCysteineFluorescence Resonance Energy TransferFluorescent DyesHumansMaleimidesProtein Conformationalpha-SynucleinCysteineFluorescent DyesmaleimideMaleimidesintrinsically disordered proteinsnative chemical ligationParkinson diseaseconvergent synthesisprotein labelingsingle moleculesmFRETthree-colorα-synuclein

Identifiers

PMID29681525
PMCPMC6014907
OpenAlexW2802996219

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.