Solution structure of a cysteine rich domain of rat protein kinase C.
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.
Hommel
U
U
SANDOZ PHARMA AG, Basel, Switzerland.
Zurini
M
M
Luyten
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D020848:Chimerin 1; D016384:Consensus Sequence; D003545:Cysteine; D019852:Diacylglycerol Kinase; D004331:Drosophila melanogaster / Q000378:metabolism; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry; D011487:Protein Conformation; D011493:Protein Kinase C / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D019908:Proto-Oncogene Proteins c-raf; D051567:Proto-Oncogene Proteins c-vav; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013552:Swine; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D020848:Chimerin 1; D005656:Fungal Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins; D012996:Solutions; C496618:VAV1 protein, human; C496620:Vav1 protein, rat; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D003545:Cysteine