An Acidic Loop and Cognate Phosphorylation Sites Define a Molecular Switch That Modulates Ubiquitin Charging Activity in Cdc34-Like Enzymes
2011

How Phosphorylation Affects Ubiquitin Charging in Cdc34-Like Enzymes

publication 10 minutes Evidence: moderate

Author Information

Author(s): Elena Papaleo, Valeria Ranzani, Farida Tripodi, Alessandro Vitriolo, Claudia Fantucci, Piercarlo Alberghina, Lilia Vanoni, Marco De Gioia, Luca Coccetti

Primary Institution: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy

Hypothesis

Does phosphorylation by CK2 modulate the activity of Cdc34-like E2 enzymes through structural changes in the acidic loop?

Conclusion

Phosphorylation of Cdc34 by CK2 enhances its ubiquitin-charging activity by stabilizing an open conformation of the acidic loop, allowing better access to the catalytic site.

Supporting Evidence

  • CK2 phosphorylation sites at S130 and S167 are crucial for the ubiquitin-charging activity of yeast Cdc34.
  • Phosphorylation stabilizes the acidic loop in an open conformation, enhancing access to the catalytic cleft.
  • Mutations in the acidic loop disrupt the enzyme's ability to charge ubiquitin effectively.

Takeaway

This study shows that a special part of a protein called the acidic loop can change shape when it gets a chemical tag called phosphate, which helps the protein do its job better.

Methodology

The study used molecular dynamics simulations and biochemical assays to investigate the effects of CK2 phosphorylation on Cdc34-like enzymes.

Limitations

The study primarily focuses on yeast Cdc34 and may not fully represent the behavior of all Cdc34-like enzymes across different organisms.

Digital Object Identifier (DOI)

10.1371/journal.pcbi.1002056

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