Evidence map›Paper›PMID 26725117›Full record

ArticleCell reports2016

Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis.

Kalyan S Chakrabarti, Roman V Agafonov, Francesco Pontiggia, Renee Otten, Matthew K Higgins, Gebhard F X Schertler, Daniel D Oprian, Dorothee Kern

Abstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
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

36 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. The Allosteric Mechanism of G-Protein-Coupled Receptors is Induced Fit, Not Conformational Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  5. Article
  6. A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025
    Review
  7. Article
  8. Contextual AI models for single-cell protein biology.bioRxiv : the preprint server for biology · 2024
    Article
  9. Ligand-induced protein transition state stabilization switches the binding pathway from conformational selection to induced fit.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Bringing the CaOpen biology · 2021
    Article
  17. Article
  18. Mechanisms of ligand binding.Biophysics reviews · 2020
    Review
  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

8 authors.

Kalyan S ChakrabartiHoward Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454; Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454.
Roman V AgafonovHoward Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454; Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454.
Francesco PontiggiaHoward Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454; Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454.
Renee OttenHoward Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454; Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454.
Matthew K HigginsDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Gebhard F X SchertlerPaul Scherrer Institute, 5232 Viligan PSI, Switzerland.
Daniel D OprianDepartment of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454. Electronic address: oprian@brandeis.edu.
Dorothee KernHoward Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454; Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454. Electronic address: dkern@brandeis.edu.

Funding

STRUCTURE/FUNCTION STUDIES OF RHODOPSINR01EY007965 · NEI · BRANDEIS UNIVERSITY · PI OPRIAN, DANIEL D · 1989 to 2017
$6.2M
STRUCTURE/FUNCTION OF COLOR VISION PIGMENTSR01EY009514 · NEI · BRANDEIS UNIVERSITY · PI OPRIAN, DANIEL D · 1992 to 2011
$2.8M
Collaborative experimental & computational studies of conformational transitionsR01GM100966 · NIGMS · BRANDEIS UNIVERSITY · PI HAGAN, MICHAEL F, KERN, DOROTHEE · 2013 to 2016
$1.2M
Howard Hughes Medical InstituteNEI NIH HHS EY009514NEI NIH HHS R01 EY007965NEI NIH HHS R01 EY009514NIGMS NIH HHS GM100966-01NIGMS NIH HHS R01 GM100966
6 · The paper itself

Abstract

Molecular recognition plays a central role in biology, and protein dynamics has been acknowledged to be important in this process. However, it is highly debated whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection) or are caused in response to ligand binding (induced fit). Proposals for both mechanisms in protein/protein recognition have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. Here, we present a direct demonstration of exclusive conformational selection in protein/protein recognition by measuring the flux for rhodopsin kinase binding to its regulator recoverin, an important molecular recognition in the vision system. Using nuclear magnetic resonance (NMR) spectroscopy, stopped-flow kinetics, and isothermal titration calorimetry, we show that recoverin populates a minor conformation in solution that exposes a hydrophobic binding pocket responsible for binding rhodopsin kinase. Protein dynamics in free recoverin limits the overall rate of binding.

Indexed as

Escherichia coliG-Protein-Coupled Receptor Kinase 1HumansNuclear Magnetic Resonance, BiomolecularProtein BindingProtein Structure, QuaternaryRecoverinG-Protein-Coupled Receptor Kinase 1RCVRN protein, humanRecoverinconformational ensembleconformational selectionenergy landscapemolecular recognition dynamicsprotein/protein interactionrecoverin

Identifiers

PMID26725117
PMCPMC4706811

What OpenQuestion holds

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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.