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A molecular basis for phosphorylation-dependent SUMO conjugation by the E2 UBC9.
Firaz Mohideen1, Allan D Capili, Parizad M Bilimoria
1Program in Structural Biology, Sloan-Kettering Institute, New York, New York, USA.
Nature Structural & Molecular Biology
|August 18, 2009
Summary
Phosphorylation enhances SUMOylation of transcription factors like MEF2 via an E2-dependent mechanism. This process is crucial for postsynaptic differentiation and various cellular pathways.
Area of Science:
- Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Post-translational modifications like phosphorylation and SUMOylation regulate protein function.
- Phosphorylation-dependent SUMO consensus motifs (PDSMs) link these two modification types.
- Myocyte-enhancement factor 2 (MEF2) is a transcription factor involved in neuronal development.
Purpose of the Study:
- To investigate the mechanism of phosphorylation-dependent SUMO conjugation.
- To determine the role of the SUMO E2 enzyme in this process.
- To assess the in vivo relevance of this mechanism in neuronal differentiation.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to study protein interactions.
- Mutational analysis of SUMO E2 enzyme.
- Biochemical assays for SUMO conjugation.
- In vivo studies using organotypic cerebellar slices.
Main Results:
- The SUMO E2 enzyme interacts with both phosphorylated and non-phosphorylated MEF2 substrates.
- A specific basic surface on the E2 enzyme enhances SUMO conjugation to phosphorylated PDSM substrates (MEF2, HSF1).
- Mutant UBC9 isoforms impairing SUMOylation of phosphorylated MEF2 also disrupt postsynaptic differentiation.
Conclusions:
- An E2-dependent mechanism facilitates phosphorylation-dependent SUMO conjugation.
- This mechanism is critical for MEF2-mediated postsynaptic differentiation.
- The findings have implications for understanding diverse cellular processes including heat-shock response and brain development.
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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
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