Abstract
Intracellular protein phosphorylation by protein kinase C (PKC) plays a major role in the translation of extracellular signals into cellular events. Speculations on the structural basis for PKC activation are based on sequence homology between their cysteine-rich domains (CRD) and the DNA-binding 'zinc-fingers'. We produced a fragment comprising the second CRD (CRD2) of rat PKC-alpha and determined its three-dimensional structure in solution by NMR spectroscopy. This revealed that CRD2 adopts a globular fold allowing two non-consecutive sets of zinc-binding residues to form two separate metal-binding sites. The fold is different to those previously proposed and allows insight into the molecular topology of a family of homologous proteins.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Cell Cycle Proteins*
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Chimerin 1
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Consensus Sequence
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Cysteine
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Diacylglycerol Kinase
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Drosophila melanogaster / metabolism
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Enzyme Activation
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Fungal Proteins / chemistry
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Humans
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Magnetic Resonance Spectroscopy
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Models, Molecular*
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / chemistry
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Protein Conformation*
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Protein Kinase C / chemistry*
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Protein Serine-Threonine Kinases / chemistry
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins c-raf
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Proto-Oncogene Proteins c-vav
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Rats
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Recombinant Fusion Proteins / chemistry
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Saccharomyces cerevisiae / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Solutions
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Swine
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Zinc Fingers
Substances
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Cell Cycle Proteins
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Chimerin 1
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Fungal Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Recombinant Fusion Proteins
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Solutions
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VAV1 protein, human
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Vav1 protein, rat
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Phosphotransferases (Alcohol Group Acceptor)
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Diacylglycerol Kinase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Protein Kinase C
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Cysteine