The Two Non-Visual Arrestins Engage ERK2 Differently.

Area of Science:

• Molecular and Cellular Biology
• Biochemistry
• Structural Biology

Background:

• Arrestins terminate G protein-coupled receptor signaling and initiate new pathways.
• Extracellular signal-regulated kinases 1/2 (ERK1/2) are key regulators of cell proliferation and survival.
• Arrestins can form complexes with ERK1/2 independently of receptors, but the molecular details are unknown.

Purpose of the Study:

• To investigate the molecular mechanisms of pairwise interactions between arrestin-2/3 and ERK1/2.
• To elucidate the structural basis for differential binding affinities between arrestins and ERK2.

Main Methods:

• Biophysical techniques
• Peptide array analysis
• Size-exclusion chromatography coupled to small-angle X-ray scattering (SEC-SAXS)

Main Results:

• Arrestin-3 binds ERK2 with higher affinity than arrestin-2.
• The differential binding is attributed to distinct molecular regions of arrestins interacting with ERK2.
• A structural model of the ERK2-arrestin-3 complex revealed conformational heterogeneity.

Conclusions:

• The distinct binding modes of arrestins to ERK2 influence the equilibrium between signaling complexes.
• Understanding these binary complexes offers potential for controlling cell fate through ERK1/2 regulation.