2cjt: Difference between revisions
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==Overview== | ==Overview== | ||
C(2) domains are well characterized as Ca(2+)/phospholipid-binding | 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== | ==About this Structure== | ||
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==Reference== | ==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 | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16732694 16732694] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Machius, M.]] | [[Category: Machius, M.]] | ||
[[Category: Rizo, J.]] | [[Category: Rizo, J.]] | ||
[[Category: Sudhof, T | [[Category: Sudhof, T C.]] | ||
[[Category: Tomchick, D | [[Category: Tomchick, D R.]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: FMT]] | [[Category: FMT]] | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:49:23 2008'' | ||
Revision as of 14:49, 21 February 2008
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STRUCTURAL BASIS FOR A MUNC13-1 HOMODIMER- MUNC13-1- RIM HETERODIMER SWITCH: C2-DOMAINS AS VERSATILE PROTEIN-PROTEIN INTERACTION MODULES
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
2CJT is a Single protein structure of sequence from Rattus norvegicus with EDO and FMT as ligands. Known structural/functional Site: AC1. 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
Page seeded by OCA on Thu Feb 21 16:49:23 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Rattus norvegicus
- Single protein
- Dai, H.
- Dulubova, I.
- Lu, J.
- Machius, M.
- Rizo, J.
- Sudhof, T C.
- Tomchick, D R.
- EDO
- FMT
- Alternative splicing
- C2 domains
- Coiled coil
- Exocytosis
- Metal-binding
- Munc13
- Neurotransmitter release
- Phorbol-ester binding
- Protein-protein interactions
- Rim
- Synaptosome
- Zinc
- Zinc finger
