Evidence map›Paper›PMID 29301968›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Engineering posttranslational proofreading to discriminate nonstandard amino acids.

Aditya M Kunjapur, Devon A Stork, Erkin Kuru, Oscar Vargas-Rodriguez, Matthieu Landon, Dieter Söll, George M Church

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Assessment of Bacterial N-Degron Proteolysis by a Dual-Fluorescence Reporter.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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  11. Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Hijacking Translation Initiation for Synthetic Biology.Chembiochem : a European journal of chemical biology · 2020
    Review
  16. Article
  17. Review
  18. The expanded specificity and physiological role of a widespread N-degron recognin.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  19. Review
  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 2 institutions in 1 country.

Aditya M KunjapurDepartment of Genetics, Harvard Medical School, Boston, MA 02115; kunjapur@alum.mit.edu dieter.soll@yale.edu gchurch@genetics.med.harvard.edu.
Devon A StorkDepartment of Genetics, Harvard Medical School, Boston, MA 02115.
Erkin KuruDepartment of Genetics, Harvard Medical School, Boston, MA 02115.
Oscar Vargas-RodriguezDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520.ORCID 0000-0002-2301-2800
Matthieu LandonDepartment of Genetics, Harvard Medical School, Boston, MA 02115.
Dieter SöllDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 kunjapur@alum.mit.edu dieter.soll@yale.edu gchurch@genetics.med.harvard.edu.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA 02115; kunjapur@alum.mit.edu dieter.soll@yale.edu gchurch@genetics.med.harvard.edu.ORCID 0000-0003-3535-2076
Harvard University · USYale University · US

Funding

TRANSFER RNAR01GM022854 · NIGMS · YALE UNIVERSITY · PI SOLL, DIETER · 1985 to 2016
$21.3M
Studies of Transfer RNAR35GM122560 · NIGMS · YALE UNIVERSITY · PI SOLL, DIETER · 2017 to 2022
$5.6M
NIGMS NIH HHS R01 GM022854NIGMS NIH HHS R35 GM122560
6 · The paper itself

Abstract

Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system called "posttranslational proofreading" to more accurately and rapidly evaluate nsAA incorporation. We achieve this proofreading by hijacking a natural pathway of protein degradation known as the N-end rule, which regulates the lifespan of a protein based on its amino-terminal residue. We find that proteins containing certain desired N-terminal nsAAs have much longer half-lives compared with those proteins containing undesired amino acids. We use the posttranslational proofreading system to further evolve a

Indexed as

Protein BiosynthesisAmino AcidsAminobiphenyl CompoundsArchaeal ProteinsEscherichia coliMethanocaldococcusProtein EngineeringProtein Processing, Post-TranslationalProteolysisTyrosine-tRNA LigaseAmino AcidsAminobiphenyl CompoundsArchaeal ProteinsTyrosine-tRNA Ligasegenetic code expansionN-end rulenonstandard amino acidsprotein degradationsynthetic biology

Identifiers

PMID29301968
PMCPMC5776986
OpenAlexW2782391402

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.