Evidence map›Paper›PMID 21532593›Full record

ArticleNature structural & molecular biology2011

Tuning protein autoinhibition by domain destabilization.

Jae-Hyun Cho, Vasant Muralidharan, Miquel Vila-Perello, Daniel P Raleigh, Tom W Muir, Arthur G Palmer

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. A Chemical Biology Primer for NMR Spectroscopists.Journal of magnetic resonance open · 2022
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Chemical exchange in biomacromolecules: past, present, and future.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2014
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. 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

6 authors at 4 institutions in 1 country.

Jae-Hyun ChoDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
Vasant Muralidharan
Miquel Vila-Perello
Daniel P Raleigh
Tom W Muir
Arthur G Palmer
Columbia University · USRockefeller University · USHoward Hughes Medical Institute · USStony Brook University · US

Funding

PROTEIN MOTIONS IN RECOGNITION, REGULATION AND CATALYSISR01GM059273 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PALMER, ARTHUR G · 1999 to 2018
$5.7M
900 MHz NMR Spectrometer for Structural BiologyP41GM066354 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI COWBURN, DAVID · 2002 to 2006
$4.7M
Regulation and Folding of a Multidomain Adaptor ProteinR01GM055843 · NIGMS · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2002 to 2009
$2.7M
Segmental Labeling for Protein Structure by NMRR01EB001991 · NIBIB · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2003 to 2007
$2.2M
Folding of Alpha-Beta Proteins at High ResolutionR01GM070941 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI RALEIGH, DANIEL P · 2004 to 2007
$1.1M
CHEMICAL BASIS OF THE SH3 DOMAIN STRUCTURER29GM055843 · NIGMS · ROCKEFELLER UNIVERSITY · PI MUIR, TOM W · 1997 to 2001
$217k
NIBIB NIH HHS EB001991NIBIB NIH HHS R01 EB001991NIGMS NIH HHS GM070941NIGMS NIH HHS GM55843NIGMS NIH HHS GM59273NIGMS NIH HHS GM66354NIGMS NIH HHS P41 GM066354NIGMS NIH HHS R01 GM055843NIGMS NIH HHS R01 GM059273NIGMS NIH HHS R01 GM070941NIGMS NIH HHS R29 GM055843
6 · The paper itself

Abstract

Activation of many multidomain signaling proteins requires rearrangement of autoinhibitory interdomain interactions that occlude activator binding sites. In one model for activation, the major inactive conformation exists in equilibrium with activated-like conformations that can be stabilized by ligand binding or post-translational modifications. We established the molecular basis for this model for the archetypal signaling adaptor protein Crk-II by measuring the thermodynamics and kinetics of the equilibrium between autoinhibited and activated-like states. We used fluorescence and NMR spectroscopies together with segmental isotopic labeling by means of expressed protein ligation. The results demonstrate that intramolecular domain-domain interactions both stabilize the autoinhibited state and induce the activated-like conformation. A combination of favorable interdomain interactions and unfavorable intradomain structural changes fine-tunes the population of the activated-like conformation and allows facile response to activators. This mechanism suggests a general strategy for optimization of autoinhibitory interactions of multidomain proteins.

Indexed as

Models, MolecularBinding SitesKineticsNuclear Magnetic Resonance, BiomolecularProtein FoldingProtein StabilityProtein Structure, TertiaryProto-Oncogene Proteins c-crkSpectrometry, FluorescenceThermodynamicsProto-Oncogene Proteins c-crk

Identifiers

PMID21532593
PMCPMC3265570
OpenAlexW2101919796

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.