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Open AccessFeature PaperArticle

Delineating the Molecular Basis of the Calmodulin–bMunc13-2 Interaction by Cross-Linking/Mass Spectrometry—Evidence for a Novel CaM Binding Motif in bMunc13-2

1
Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Charles Tanford Protein Center, Martin Luther University Halle-Wittenberg, D-06120 Halle/Saale, Germany
2
Center for Structural Biology, Department of Chemistry, Vanderbilt University, Nashville, TN 37221, USA
3
Biophysical Chemistry, Institute of Chemistry, Martin Luther University Halle-Wittenberg, D-06120 Halle/Saale, Germany
4
Proteomics Group, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
5
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
*
Authors to whom correspondence should be addressed.
Present address: Serumwerk Bernburg AG, D-06406 Bernburg, Germany.
Cells 2020, 9(1), 136; https://doi.org/10.3390/cells9010136 (registering DOI)
Received: 21 November 2019 / Revised: 23 December 2019 / Accepted: 2 January 2020 / Published: 7 January 2020
(This article belongs to the Special Issue 25 Years of Proteomics in Cell Biology)
Exploring the interactions between the Ca2+ binding protein calmodulin (CaM) and its target proteins remains a challenging task. Members of the Munc13 protein family play an essential role in short-term synaptic plasticity, modulated via the interaction with CaM at the presynaptic compartment. In this study, we focus on the bMunc13-2 isoform expressed in the brain, as strong changes in synaptic transmission were observed upon its mutagenesis or deletion. The CaM–bMunc13-2 interaction was previously characterized at the molecular level using short bMunc13-2-derived peptides only, revealing a classical 1–5–10 CaM binding motif. Using larger protein constructs, we have now identified for the first time a novel and unique CaM binding site in bMunc13-2 that contains an N-terminal extension of a classical 1–5–10 CaM binding motif. We characterize this motif using a range of biochemical and biophysical methods and highlight its importance for the CaM–bMunc13-2 interaction. View Full-Text
Keywords: Munc13; calmodulin; cross-linking; mass spectrometry; proteinprotein interaction Munc13; calmodulin; cross-linking; mass spectrometry; proteinprotein interaction
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Piotrowski, C.; Moretti, R.; Ihling, C.H.; Haedicke, A.; Liepold, T.; Lipstein, N.; Meiler, J.; Jahn, O.; Sinz, A. Delineating the Molecular Basis of the Calmodulin–bMunc13-2 Interaction by Cross-Linking/Mass Spectrometry—Evidence for a Novel CaM Binding Motif in bMunc13-2. Cells 2020, 9, 136.

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