Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding
2011
How Phosphorylation Affects Munc18a's Ability to Bind Syntaxin
publication
Evidence: high
Author Information
Author(s): Bar-On Dana, Nachliel Esther, Gutman Menachem, Ashery Uri
Primary Institution: Tel Aviv University
Hypothesis
The reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins.
Conclusion
The study reveals that phosphorylation induces a closed-cavity conformation in munc18a, making it less able to bind to syntaxin.
Supporting Evidence
- The study shows that wild-type munc18a exists in a dynamic equilibrium between several conformations.
- Phosphomimetic mutations lead to a rigid closed-cavity conformation in munc18a.
- The closed-cavity conformation makes syntaxin binding energetically unfavorable.
- Cluster analysis indicates that the phosphomimetic mutant samples fewer conformations than the wild-type.
Takeaway
When a protein called munc18a gets a chemical tag called phosphate, it changes shape and can't grab onto another protein called syntaxin as easily.
Methodology
The study used molecular dynamics simulations to explore the dynamics of wild-type and phosphomimetic mutant munc18a.
Digital Object Identifier (DOI)
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