1y8f
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(New page: 200px<br /><applet load="1y8f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y8f" /> '''Solution structure of the munc13-1 C1-domain...)
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Revision as of 04:30, 21 November 2007
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Solution structure of the munc13-1 C1-domain
Overview
Protein kinase C (PKC) isozymes and other receptors of diacylglycerol, (DAG) bind to this widespread second messenger through their C(1) domains., These alternative DAG receptors include munc13-1, a large neuronal protein, that is crucial for DAG-dependent augmentation of neurotransmitter, release. Whereas the structures of several PKC C(1) domains have been, determined and have been shown to require little conformational changes, for ligand binding, it is unclear whether the C(1) domains from other DAG, receptors contain specific structural features with key functional, significance. To gain insight into this question, we have determined the, three-dimensional structure in solution of the munc13-1 C(1) domain using, NMR spectroscopy. The overall structure includes two beta-sheets, a short, C-terminal alpha-helix, and two Zn(2+)-binding sites, resembling the, structures of PKC C(1) domains. However, the munc13-1 C(1) domain exhibits, striking structural differences with the PKC C(1) domains in the, ligand-binding site. These differences result in occlusion of the binding, site of the munc13-1 C(1) domain by a conserved tryptophan side chain that, in PKCs adopts a completely different orientation. As a consequence, the, munc13-1 C(1) domain requires a considerable conformational change for, ligand binding. This structural distinction is expected to decrease the, DAG affinity of munc13-1 compared to that of PKCs, and is likely to be, critical for munc13-1 function. On the basis of these results, we propose, that augmentation of neurotransmitter release may be activated at higher, DAG levels than PKCs as a potential mechanism for uncoupling augmentation, of release from the multitude of other signaling processes mediated by, DAG.
About this Structure
1Y8F is a Single protein structure of sequence from Rattus norvegicus with ZN as ligand. Full crystallographic information is available from OCA.
Reference
Intramolecular occlusion of the diacylglycerol-binding site in the C1 domain of munc13-1., Shen N, Guryev O, Rizo J, Biochemistry. 2005 Feb 1;44(4):1089-96. PMID:15667202
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