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Related Concept Videos

Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Fusion of Secretory Vesicles with the Plasma Membrane01:26

Fusion of Secretory Vesicles with the Plasma Membrane

Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
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Energy to Drive Translocation

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Related Experiment Video

Updated: Jun 3, 2026

In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal
06:45

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Dynamic conformational changes in munc18 prevent syntaxin binding.

Dana Bar-On1, Esther Nachliel, Menachem Gutman

  • 1Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel.

Plos Computational Biology
|March 11, 2011
PubMed
Summary
This summary is machine-generated.

Phosphorylation of munc18a by Protein Kinase C changes its structure, reducing binding to syntaxin-1a. This study reveals a closed-cavity conformation, not electrostatic repulsion, explains reduced affinity in vesicle fusion.

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Related Experiment Videos

Last Updated: Jun 3, 2026

In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal
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Published on: January 14, 2018

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Published on: August 2, 2019

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Published on: May 12, 2023

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The Sec1/munc18 protein family regulates vesicle fusion by interacting with SNARE proteins.
  • Protein kinase C (PKC) phosphorylates munc18a, decreasing its affinity for syntaxin-1a, a key SNARE member.
  • Current hypothesis attributes reduced affinity to electrostatic repulsion between phosphorylated munc18a and syntaxin-1a.

Purpose of the Study:

  • To challenge the established hypothesis regarding munc18a-syntaxin-1a interaction modulation by phosphorylation.
  • To elucidate the novel mechanism behind reduced munc18a affinity to syntaxin-1a upon phosphorylation.
  • To investigate the conformational changes in munc18a induced by phosphomimetic mutations.

Main Methods:

  • Utilized molecular dynamics (MD) simulations to compare wild-type munc18a and phosphomimetic mutant munc18a.
  • Focused analysis on the structural dynamics of the cavity between domains 3a and 1, the primary syntaxin-binding site.
  • Examined residue interactions within the munc18a cavity to understand conformational changes.

Main Results:

  • Wild-type munc18a exists in a dynamic equilibrium of conformations with varying cavity sizes, facilitating syntaxin binding.
  • Phosphomimetic mutations induced a rigid, closed-cavity conformation in munc18a.
  • This closed conformation results from specific residue interactions, sterically and energetically hindering syntaxin binding.

Conclusions:

  • Reduced affinity of phosphorylated munc18a to syntaxin-1a is due to a closed-cavity conformation, not electrostatic repulsion.
  • Phosphorylation acts as a key driver for significant protein conformational changes, modulating target protein affinity.
  • This finding offers a new mechanistic understanding of munc18a regulation in vesicle fusion.