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Structural insights into calmodulin/Munc13 interaction

  • Sabine Herbst EMAIL logo , Noa Lipstein , Olaf Jahn und Andrea Sinz EMAIL logo
Veröffentlicht/Copyright: 17. April 2014

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.


Corresponding authors: Sabine Herbst and Andrea Sinz, Institute of Pharmacy, Department of Pharmaceutical Chemistry and Bioanalytics, Martin-Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, D-06120 Halle/Saale, Germany, e-mail: ;

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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Received: 2014-2-14
Accepted: 2014-4-11
Published Online: 2014-4-17
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

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