Detailed Regulatory Mechanism of the Interaction between ZO-1 PDZ2 and Connexin43 Revealed by MD Simulations
2011

Understanding How Connexin43 Binds to ZO-1 PDZ2

publication Evidence: moderate

Author Information

Author(s): Xiao Fei, Weng Jingwei, Fan Kangnian, Wang Wenning

Primary Institution: Fudan University

Hypothesis

How do the interactions between ZO-1 PDZ2 and connexin43 peptides vary with peptide length and phosphorylation?

Conclusion

The study reveals that phosphorylation at Ser(-9) significantly weakens the binding of connexin43 to ZO-1 PDZ2.

Supporting Evidence

  • The binding of connexin43 to ZO-1 PDZ2 is mediated by its C-terminal tail.
  • Phosphorylation at Ser(-9) disrupts the binding of connexin43 to ZO-1 PDZ2.
  • Longer peptides of connexin43 show higher binding affinity to ZO-1 PDZ2.

Takeaway

This study shows that a protein called connexin43 can stick to another protein called ZO-1, but if a tiny part of connexin43 gets changed (phosphorylated), it can't stick as well anymore.

Methodology

Molecular dynamics simulations were used to study the interactions between ZO-1 PDZ2 and different lengths of connexin43 peptides.

Limitations

The simulations may not fully capture the conformational spaces of the peptides due to the initial structures not being 'native'.

Digital Object Identifier (DOI)

10.1371/journal.pone.0021527

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