Abstract
Munc13 proteins are essential presynaptic regulators that mediate synaptic vesicle priming and play a role in the regulation of neuronal short-term synaptic plasticity. All four Munc13 isoforms share a common domain structure, including a calmodulin (CaM) binding site in their otherwise divergent N-termini. Here, we summarize recent results on the investigation of the CaM/Munc13 interaction. By combining chemical cross-linking, photoaffinity labeling, and mass spectrometry, we showed that all neuronal Munc13 isoforms exhibit similar CaM binding modes. Moreover, we demonstrated that the 1-5-8-26 CaM binding motif discovered in Munc13-1 cannot be induced in the classical CaM target skMLCK, indicating unique features of the Munc13 CaM binding motif.
Acknowledgments
SH gratefully acknowledges funding from the DFG-Graduiertenkolleg GRK 1026 “Conformational Transitions in Macromolecular Interactions”. The authors are indebted to Dr Christian Ihling for liquid chromatography/MS analysis, to Dr Stefan Kalkhof for modeling studies, to Marian Schneider for SPR experiments, and to Daniel Maucher for assistance with cross-linking experiments. We thank Professor Nils Brose for continuous support.
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©2014 by Walter de Gruyter Berlin/Boston
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: conformational transitions in macromolecular interactions
- Single-molecule spectroscopy of unfolded proteins and chaperonin action
- Influence of the polypeptide environment next to amyloidogenic peptides on fibril formation
- Structure of large dsDNA viruses
- Functional aspects of extracellular cyclophilins
- Generic tools for conditionally altering protein abundance and phenotypes on demand
- Structural insights into calmodulin/Munc13 interaction
- Interaction of linear polyamines with negatively charged phospholipids: the effect of polyamine charge distance
- Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity
- Lanthanides as substitutes for calcium ions in the activation of plant α-type phospholipase D
- Insights from reconstitution reactions of COPII vesicle formation using pure components and low mechanical perturbation
- Identification of key residues in the formate channel FocA that control import and export of formate
- Twin-arginine translocation-arresting protein regions contact TatA and TatB
- Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
- An ancient oxidoreductase making differential use of its cofactors
- Biophysical characterization of polyomavirus minor capsid proteins
- Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
- Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
- Thermodynamic signatures in macromolecular interactions involving conformational flexibility
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: conformational transitions in macromolecular interactions
- Single-molecule spectroscopy of unfolded proteins and chaperonin action
- Influence of the polypeptide environment next to amyloidogenic peptides on fibril formation
- Structure of large dsDNA viruses
- Functional aspects of extracellular cyclophilins
- Generic tools for conditionally altering protein abundance and phenotypes on demand
- Structural insights into calmodulin/Munc13 interaction
- Interaction of linear polyamines with negatively charged phospholipids: the effect of polyamine charge distance
- Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity
- Lanthanides as substitutes for calcium ions in the activation of plant α-type phospholipase D
- Insights from reconstitution reactions of COPII vesicle formation using pure components and low mechanical perturbation
- Identification of key residues in the formate channel FocA that control import and export of formate
- Twin-arginine translocation-arresting protein regions contact TatA and TatB
- Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
- An ancient oxidoreductase making differential use of its cofactors
- Biophysical characterization of polyomavirus minor capsid proteins
- Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
- Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
- Thermodynamic signatures in macromolecular interactions involving conformational flexibility