Evidence map›Paper›PMID 30156841›Full record

ArticleJournal of the American Chemical Society2018

An Atypical Mechanism of Split Intein Molecular Recognition and Folding.

Adam J Stevens, Giridhar Sekar, Josef A Gramespacher, David Cowburn, Tom W Muir

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. A Unique THN Motif Is Critical for Enabling Efficient C-Terminal Traceless Cleavage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Live-cell protein engineering with an ultra-short split intein.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Review
  16. A mesophilic cysteine-less split intein for proteinProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  17. Proximity Induced Splicing Utilizing Caged Split Inteins.Journal of the American Chemical Society · 2019
    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

5 authors at 2 institutions in 1 country.

Adam J StevensDepartment of Chemistry, Frick Laboratory , Princeton University , Princeton , New Jersey 08544 , United States.
Giridhar SekarDepartment of Biochemistry , Albert Einstein College of Medicine , Bronx , New York 10461 , United States.
Josef A GramespacherDepartment of Chemistry, Frick Laboratory , Princeton University , Princeton , New Jersey 08544 , United States.
David CowburnDepartment of Biochemistry , Albert Einstein College of Medicine , Bronx , New York 10461 , United States.ORCID 0000-0001-6770-7172
Tom W MuirDepartment of Chemistry, Frick Laboratory , Princeton University , Princeton , New Jersey 08544 , United States.ORCID 0000-0001-9635-0344
Princeton University · USAlbert Einstein College of Medicine · US

Funding

Structure, Function and Applications of InteinsR37GM086868 · NIGMS · PRINCETON UNIVERSITY · PI MUIR, TOM · 2012 to 2021
$5.4M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR015495 · NCRR · NEW YORK STRUCTURAL BIOLOGY CENTER · PI RIFKIND, RICHARD A · 2000 to 2000
$2.0M
Upgrade of 800 MHz SpectrometerS10OD016432 · OD · NEW YORK STRUCTURAL BIOLOGY CENTER · PI PALMER, ARTHUR G · 2014 to 2014
$600k
Console and probe upgrade for 600 MHz NMRS10OD016305 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI COWBURN, DAVID · 2014 to 2014
$595k
NCRR NIH HHS C06 RR015495NIGMS NIH HHS R37 GM086868NIH HHS S10 OD016305NIH HHS S10 OD016432
6 · The paper itself

Abstract

Split inteins associate to trigger protein splicing in trans, a post-translational modification in which protein sequences fused to the intein pair are ligated together in a traceless manner. Recently, a family of naturally split inteins has been identified that is split at a noncanonical location in the primary sequence. These atypically split inteins show considerable promise in protein engineering applications; however, the mechanism by which they associate is unclear and must be different from that of previously characterized canonically split inteins due to unique topological restrictions. Here, we use a consensus design strategy to generate an atypical split intein pair (Cat) that has greatly improved activity and is amenable to detailed biochemical and biophysical analysis. Guided by the solution structure of Cat, we show that the association of the fragments involves a disorder-to-order structural transition driven by hydrophobic interactions. This molecular recognition mechanism satisfies the topological constraints of the intein fold and, importantly, ensures that premature chemistry does not occur prior to fragment complementation. Our data lead a common blueprint for split intein complementation in which localized structural rearrangements are used to drive folding and regulate protein-splicing activity.

Indexed as

Amino Acid SequenceHydrophobic and Hydrophilic InteractionsInteinsModels, MolecularProtein FoldingProteinsProtein SplicingSequence AlignmentProteins

Identifiers

PMID30156841
PMCPMC7232844
OpenAlexW2888842790

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.