2cjs | pdb_00002cjs
STRUCTURAL BASIS FOR A MUNC13-1 HOMODIMER- MUNC13-1- RIM HETERODIMER SWITCH: C2-DOMAINS AS VERSATILE PROTEIN-PROTEIN INTERACTION MODULES
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| 2cjs, resolution 1.78Å | |||||||||||||
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| Sites: | AC1 | ||||||||||||
| Ligands: | ZN, EDO and GOL | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
C(2) domains are well characterized as Ca(2+)/phospholipid-binding modules, but little is known about how they mediate protein-protein interactions. In neurons, a Munc13-1 C(2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13-1 C(2)A domain homodimerizes, and that homodimerization competes with Munc13-1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13-1 C(2)A-domain homodimer and the Munc13-1 C(2)A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively. The C(2)A domain adopts a beta-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded beta-barrel. In contrast, heterodimerization involves the bottom tip of the C(2)A-domain beta-sandwich and a C-terminal alpha-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13-1 homodimer-Munc13-1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C(2) domains as protein-protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes.
About this Structure
2CJS is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch., Lu J, Machius M, Dulubova I, Dai H, Sudhof TC, Tomchick DR, Rizo J, PLoS Biol. 2006 Jul;4(7):e192. PMID:16732694
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Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Protein complex
- Rattus norvegicus
- Dai, H.
- Dulubova, I.
- Lu, J.
- Machius, M.
- Rizo, J.
- Sudhof, T C.
- Tomchick, D R.
- EDO
- GOL
- ZN
- Alternative splicing
- C2 domain
- Coiled coil
- Exocytosis
- Metal-binding
- Munc13
- Neurotransmitter release
- Neurotransmitter transport
- Phorbol-ester binding
- Protein-protein interaction
- Rim
- Synapse
- Synaptosome
- Transport
- Zinc
- Zinc finger
