– Document – 14-3-3 proteins in the nervous system anoxia medical definition

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Author(s): daniela berg (corresponding author) [1, 2]; carsten holzmann [3]; olaf riess [1] 14-3-3 proteins — signalling molecules that were initially described as activators of neurotransmitter synthesis — have been shown to interact with various protein kinases, receptor proteins, enzymes, structural and cytoskeletal proteins, proteins involved in cell cycle and transcriptional control, and proteins involved in apoptosis [1]. The function of 14-3-3 proteins in these cellular processes is not entirely clear yet. However, it has become obvious that they not only regulate the activity of enzymes, but also control the subcellular localization of proteins and function as adaptor molecules, stimulating protein-protein interactions [1, 2, 3]. 14-3-3 proteins received their name in 1967 during a systematic classification of brain proteins that was based on their fraction number after diethylaminoethyl (DEAE)-CELLULOSE CHROMATOGRAPHY and their position after subsequent STARCH-GEL ELECTROPHORESIS [4].Anoxia medical definition


this class of proteins have been found in all eukaryotic organisms studied so far [2]. There are seven known mammalian 14-3-3 isotypes ([beta], [gamma], [epsilon], [eta];, [zeta], [sigma] and [tau]/[theta]) [5]. The species initially designated as [alpha] and [delta] are the phosphorylated forms of [beta] and [zeta] (ref. 6) (table 1). The highest tissue concentration of 14-3-3 proteins is found in the brain, comprising about 1% of its total soluble protein [7, 8, 9] and being present in the cytoplasmic compartment, plasma membrane and in intracellular organelles [10]. In addition to their possible role in neuronal function, 14-3-3 proteins have attracted much recent interest owing to their possible involvement in the pathophysiology of various neurological disorders.Anoxia medical definition structural information X-ray diffraction of the [zeta] and [tau] mammalian isotypes revealed a cup-shaped dimeric structure of 14-3-3 proteins [11, 12], with each monomer containing nine [alpha]-helices organized in an antiparallel manner to form an L-shaped structure (fig. 1). The interior of this structure consists of two helices with many charged and polar amino acids ([alpha]C and [alpha]E) and two with hydrophobic amino acids ([alpha]G and [alpha]I), forming a highly conserved concave amphipathic groove — the site of interaction of 14-3-3 proteins with phosphorylated and non-phosphorylated ligands [13, 14]. The protein sequence of 14-3-3 proteins consists of five highly conserved blocks that are separated by less conserved regions [15].Anoxia medical definition the conserved blocks contain residues that are important for peptide binding and some residues that are involved in dimerization [16, 17]. The carboxyl (C) termini of 14-3-3 proteins show little sequence conservation. This carboxyl tail is thought to regulate the function of 14-3-3 proteins or to stabilize the unbound structure by interaction with the two internal grooves of the 14-3-3 dimer [11]. Several motifs that are important for 14-3-3 binding have been identified. Many of them contain phosphoserine/threonine consensus sequences that are recognized by all 14-3-3 protein subtypes [18, 19]. These motifs, however, do not seem to be solely responsible for binding, as other parts of the protein can additionally modulate 14-3-3 binding [2].Anoxia medical definition increased ligand binding was shown [20] by using a truncated mutant of 14-3-3[zeta] in which the C-terminal tail had been removed. This finding…