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Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
Structural basis of protein phosphatase 2A stable latency
Li Jiang1, Vitali Stanevich, Kenneth A Satyshur
1McArdle Laboratory, Department of Oncology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Nature Communications
|April 18, 2013
Summary
Protein phosphatase 2A catalytic subunit (PP2Ac) is stabilized by the regulatory protein α4, which is essential for cell survival. This study reveals how α4 binding induces structural changes to regulate PP2A complexes and cell survival.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein phosphatase 2A (PP2A) is crucial for cellular functions.
- The catalytic subunit (PP2Ac) requires regulatory subunits for stability and function.
- α4 is an essential regulatory protein for PP2A complex biogenesis and cell survival.
Purpose of the Study:
- To elucidate the structural basis of α4 binding to PP2Ac.
- To understand the mechanism by which α4 regulates PP2A activity and stability.
- To investigate the role of the PP2Ac-α4 interaction in cell survival.
Main Methods:
- X-ray crystallography to determine the structure of α4 bound to PP2Ac N-terminal fragment.
- Allosteric modeling to predict conformational changes in full-length PP2Ac.
- Biochemical assays to assess PP2A ubiquitination and complex formation.
Main Results:
- The structure reveals α4 binding induces local unfolding near the PP2Ac active site.
- This binding allosterically perturbs the scaffold subunit binding site, stabilizing an inactive PP2Ac conformation.
- The PP2Ac-α4 interface is vital for cell survival and prevents PP2A ubiquitination, enhancing stability.
Conclusions:
- α4 acts as a scavenger chaperone, stabilizing latent PP2Ac.
- α4 regulates cell survival through its interaction with PP2Ac.
- α4 plays a key role in the biogenesis and quality control of PP2A holoenzymes.
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