2KDU

Structural basis of the Munc13-1/Ca2+-Calmodulin interaction: A novel 1-26 calmodulin binding motif with a bipartite binding mode

Summary for 2KDU

• Entry DOI: 10.2210/pdb2kdu/pdb
• Descriptor: Calmodulin, Protein unc-13 homolog A, CALCIUM ION (3 entities in total)
• Functional Keywords: protein, calmodulin, munc13, calcium, acetylation, methylation, alternative splicing, cell junction, cell membrane, coiled coil, cytoplasm, exocytosis, membrane, metal-binding, phorbol-ester binding, phosphoprotein, synapse, zinc, zinc-finger, metal binding protein-protein binding complex, metal binding protein-exocytosis complex, metal binding protein/exocytosis
• Biological source: Xenopus laevis (clawed frog,common platanna,platanna)
• Cellular location: Cytoplasm: Q62768
• Total number of polymer chains: 2
• Total formula weight: 21058.49

Authors

Rodriguez-Castaneda, F.A.,Maestre-Martinez, M.,Coudevylle, N.,Dimova, K.,Jahn, O.,Junge, H.,Becker, S.,Brose, N.,Carlomagno, T.,Griesinger, C. (deposition date: 2009-01-19, release date: 2009-12-15, Last modification date: 2024-05-22)

Primary citation

Rodriguez-Castaneda, F.,Maestre-Martinez, M.,Coudevylle, N.,Dimova, K.,Junge, H.,Lipstein, N.,Lee, D.,Becker, S.,Brose, N.,Jahn, O.,Carlomagno, T.,Griesinger, C.
Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.
Embo J., 29:680-691, 2010

PubMed Abstract: Ca(2+) signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca(2+)-CaM binds a conserved region in the priming proteins Munc13-1 and ubMunc13-2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca(2+) signals. We solved the structure of Ca(2+)(4)-CaM in complex with the CaM-binding domain of Munc13-1, which features a novel 1-5-8-26 CaM-binding motif with two separated mobile structural modules, each involving a CaM domain. Photoaffinity labelling data reveal the same modular architecture in the complex with the ubMunc13-2 isoform. The N-module can be dissociated with EGTA to form the half-loaded Munc13/Ca(2+)(2)-CaM complex. The Ca(2+) regulation of these Munc13 isoforms can therefore be explained by the modular nature of the Munc13/Ca(2+)-CaM interactions, where the C-module provides a high-affinity interaction activated at nanomolar [Ca(2+)](i), whereas the N-module acts as a sensor at micromolar [Ca(2+)](i). This Ca(2+)/CaM-binding mode of Munc13 likely constitutes a key molecular correlate of the characteristic Ca(2+)-dependent modulation of short-term synaptic plasticity.

PubMed: 20010694
DOI: 10.1038/emboj.2009.373

Experimental method

SOLUTION NMR