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2cjt
From Proteopedia
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==Overview== | ==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 .. | + | 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== | ||
| - | 2CJT is a | + | 2CJT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with EDO and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CJT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:55:53 2007'' |
Revision as of 12:50, 5 November 2007
|
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. Structure known Active 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 Jun;4(7):e192. PMID:16732694
Page seeded by OCA on Mon Nov 5 14:55:53 2007
Categories: 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
