5UE8

The crystal structure of Munc13-1 C1C2BMUN domain

Summary for 5UE8

• Entry DOI: 10.2210/pdb5ue8/pdb
• Related: 5UF7
• Descriptor: Protein unc-13 homolog A, ZINC ION, CHLORIDE ION (3 entities in total)
• Functional Keywords: alpha helical, neurotransmitter release, snare motif, exocytosis, c1 domain, c2 domain
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasm: Q62768
• Total number of polymer chains: 2
• Total formula weight: 219736.85

Authors

Tomchick, D.R.,Rizo, J.,Xu, J. (deposition date: 2016-12-29, release date: 2017-02-15, Last modification date: 2024-10-30)

Primary citation

Xu, J.,Camacho, M.,Xu, Y.,Esser, V.,Liu, X.,Trimbuch, T.,Pan, Y.Z.,Ma, C.,Tomchick, D.R.,Rosenmund, C.,Rizo, J.
Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN.
Elife, 6:-, 2017

PubMed Abstract: Munc13-1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13-1 are coordinated. The crystal structure of a Munc13-1 fragment including its C, CB and MUN domains (CCBMUN) reveals a 19.5 nm-long multi-helical structure with the C and CB domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca-binding sites of the C and CB domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13-1 by Ca and diacylglycerol during short-term presynaptic plasticity are closely interrelated. Electrophysiological experiments in mouse neurons support the functional importance of the domain interfaces observed in CCBMUN. The structure imposes key constraints for models of neurotransmitter release and suggests that Munc13-1 bridges the vesicle and plasma membranes from the periphery of the membrane-membrane interface.

PubMed: 28177287
DOI: 10.7554/eLife.22567

Experimental method

X-RAY DIFFRACTION (3.35 Å)