Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Protein-protein Interfaces02:04

Protein-protein Interfaces

14.4K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.4K
Protein-Protein Interfaces02:04

Protein-Protein Interfaces

4.4K
4.4K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.6K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.6K
2.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

3.0K
3.0K
Conserved Binding Sites01:49

Conserved Binding Sites

5.0K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Local sequence context determines the effect of glycine substitutions in collagen triple helices.

Biophysical journal·2026
Same author

Dynamical modeling of individual sensory reactivity and habituation learning.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

ERK inhibits Capicua repressor function via multisite phosphorylation.

Journal of cell science·2026
Same author

Optogenetic control of transition to metamorphosis.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Disrupted developmental signaling induces novel transcriptional states.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

A model for boundary-driven tissue morphogenesis.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
Same journal

PAX8 controls proximal tubule epithelial identity and stress response through epigenetic modification of distal regulatory elements.

The Journal of biological chemistry·2026
See all related articles

Related Experiment Video

Updated: Jan 17, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.2K

Asymmetric coevolution of the MEK-ERK binding interface.

Anton V Persikov1, Robert A Marmion2, Stanislav Y Shvartsman3

  • 1Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

The Journal of Biological Chemistry
|September 13, 2025
PubMed
Summary
This summary is machine-generated.

The study reveals how the MEK protein's adaptable docking site (D-site) coevolves with ERK, balancing conserved function with signaling flexibility. This adaptable motif is crucial for MEK-ERK complex stability and signaling dynamics.

Keywords:
MEKcoevolutionkinaseprotein bindingshort linear motif

More Related Videos

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
13:02

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO

Published on: December 28, 2019

7.9K
Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions
10:44

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions

Published on: October 21, 2016

31.6K

Related Experiment Videos

Last Updated: Jan 17, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.2K
Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
13:02

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO

Published on: December 28, 2019

7.9K
Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions
10:44

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions

Published on: October 21, 2016

31.6K

Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • Extracellular signal-regulated kinase (ERK) is a highly conserved protein regulating cellular processes via phosphorylation.
  • Mitogen-activated protein kinase kinase (MEK) phosphorylates ERK, but its interaction network is less complex.
  • The asymmetry in protein-protein interaction networks may influence coevolution.

Purpose of the Study:

  • To investigate the coevolution of the MEK-ERK complex.
  • To understand the role of MEK's intrinsically disordered N-terminal docking motif (D-site) in MEK-ERK interactions.
  • To explore how evolutionary pressures shape protein-protein interaction networks.

Main Methods:

  • Phylogenetic sequence analysis across metazoan species.
  • Structure prediction using AlphaFold2.
  • Molecular dynamics simulations.
  • Functional assays in Drosophila melanogaster.

Main Results:

  • MEK's D-site showed accelerated divergence, while ERK remained conserved.
  • Five conserved D-site residues form stable contacts with ERK's D-recruitment site.
  • D-site interactions are essential for downstream signaling and exhibit an allosteric role.
  • The D-site is conserved within groups but diverges across them, indicating evolutionary adaptation.

Conclusions:

  • MEK utilizes a simple, adaptable D-site motif to regulate MEK-ERK complex stability and binding dynamics.
  • Evolutionary pressures drive a balance between functional conservation and signaling adaptability in the MEK-ERK interaction.
  • This study demonstrates a combined approach to study protein-protein interaction network evolution.