Proteins posttranslational processing

The shell of all picomaviruses is built up from 60 copies each of four polypeptide chains, called VPl to VP4. These are translated from the viral RNA into a single polypeptide, which is posttranslationally processed by stepwise proteolysis involving viraily encoded enzymes. First, the polypeptide chain is cleaved into three proteins VPO (which is the precursor for VP2 and VP4), VPl and VP3. These proteins begin the assembly process. The last step of the processing cascade occurs during completion of the virion assembly the precursor protein VPO is cleaved into VP2 and VP4 by a mechanism that is probably autocatalytic but may also involve the viral RNA. VPl, VP2, and VP3 have molecular masses of around 30,000 daltons, whereas VP4 is small, being 7000 daltons, and is completely buried inside the virion. 

Mitochondria are unique organelles in that they contain their own DNA (mtDNA), which, in addition to ribosomal RN A (rRNA) and transfer RN A (tRNA)-coding sequences, also encodes 13 polypeptides which are components of complexes I, III, IV, and V (Anderson et al., 1981). This fact has important implications for both the genetics and the etiology of the respiratory chain disorders. Since mtDNA is maternally-inherited, a defect of a respiratory complex due to a mtDNA deletion would be expected to show a pattern of maternal transmission. However the situation is complicated by the fact that the majority of the polypeptide subunits of complexes I, III, IV, and V, and all subunits of complex II, are encoded by nuclear DNA. A defect in a nuclear-coded subunit of one of the respiratory complexes would be expected to show classic Mendelian inheritance. A further complication exists in that it is now established that some respiratory chain disorders result from defects of communication between nuclear and mitochondrial genomes (Zeviani et al., 1989). Since many mitochondrial proteins are synthesized in the cytosol and require a sophisticated system of posttranslational processing for transport and assembly, it is apparent that a diversity of genetic errors is to be expected. 

COLLAGEN ILLUSTRATES THE ROLE OF POSTTRANSLATIONAL PROCESSING IN PROTEIN MATURATION... 

POSTTRANSLATIONAL PROCESSING AFFECTS THE ACTIVITY OF MANY PROTEINS... 

Nauseef, W. M. (1987). Posttranslational processing of a human myeloid lysosomal protein, myeloperoxidase. Blood 70,1143-50. 

The majority of cases of cystic fibrosis result from deletion of phenylalanine at position 508 (AF508), which interferes with proper protein folding and the posttranslational processing of oligosaccharide side chains. The abnormal chloride channel protein (CFTR) is degraded by the cytosolic proteasome complex rather than being translocated to the cell membrane. Other functional defects in CFTR protein that teaches the cell membrane may also contribute to the pathogenesis of cystic fibrosis. 

Slobodyansky E, Berkovich A, Bovolin P, et al The endogenous allosteric modulation of GABA-A receptor subtypes a role for the neuronal posttranslational processing products of rat brain DBl, in GABA and Benzodiazepine Receptor Subtypes. Edited by Biggio G, Costa E. New York, Raven, 1990, p 52 Small DH, Nurcombe V, Moir R Association and release of the amyloid protein precursor of Alzheimer s disease from chick brain extracellular matrix. J Neurosci 12 4143-4150, 1992... 

The protein posttranslational modifications (PTMs) play a crucial role in modifying the end product of expression and contribute towards biological processes and diseased conditions. Important posttranslational modifications include phosphorylation, acetylation, glycosylation, ubiquitination, and nitration [Mann and Jensen, 2003], The analysis of posttranslational modifications on a proteome scale is still considered an analytical challenge [Zhou et al., 2001] because of the extremely low abundance of modified proteins among very complex proteome samples. 

Prenylated proteins have characteristic C-terminal sequences. For example, the three allelic Ras proteins (H-Ras, K-Ras, and N-Ras) expressed in mammalian tissues contain a C-terminal tetrapeptide which begins with cysteine, and ends with either methionine or serine. This part of the molecule is referred to as the CaaX box where C = cysteine, a = an aliphatic amino acid, and X = a prenylation specificity residue. The first step in the posttranslational processing of Ras proteins utilizes FTase and farnesyl diphosphate (FPP) to covalently attach a farnesyl group to the cysteine thiol of the CaaX box. While subsequent processing events involve proteolytic removal of the aaX tripeptide and methylation of the resulting C-termi-nal carboxylate group, only the farnesyl modification is required for mutant Ras proteins to associate with the cell membrane and transform a cell.2-6... 

Notes Inhibition of posttranslational processing of v-Ras protein in cultured RAT-1 cells. b-ND = not-determined... 

Formation of TPQ in the amine oxidases in which it occurs is initiated by binding of Cu to the precursor protein at the same site in which it functions as cofactor in the mature enzyme. Subsequently, the specific tyrosyl residue, the second amino acid in the conserved sequence Asn-Tyr-(Asp/Glu)-Tyr [44], is converted into TPQ in several steps, with the Cu catalyzing the oxidation of the precursor by 02 [45], Indications exist that this autocatalytic process is sometimes suboptimal most probably the insufficient availability of Cu and/or 02 in the posttranslational process is responsible [46],... 

To evaluate the actual protein levels ofpeptide synthetases with respect to translation, posttranslational processing, stability, and localization. These aspects are especially related to the compartmentation of eukaryotic cells. So far, evidence for a vacuolar attachment of ACV synthetase in P. chrysogenum has been obtained [95], but it has not been fully substantiated in further studies [96], The synthetase is now considered to be cytoplasmatic. 

The mechanism of N-acetylation of a-crystallin is quite interesting. The N-terminal residue has been identified as N-acetyl methionine. This methionine residue is derived from Met-tRNA et which is responsible for the initiation of the polypeptide chain and not Met-tRNAmet which incorporates the methionine residue in the growing polypeptide chain. It is clear that the N-acetylation is a true posttranslational process since acetyl Met-tRNA cannot replace formyl Met-tRNA et. Moreover, N-acetylation occurs when the polypeptide chain has reached a length consisting of approximately 25 amino acid residues. Other proteins, such as ovalbumin, are also acetylated during the early stages of polymerization on the polysome, and the protein acetyltransferase activity must therefore be associated with the protein-synthesizing apparatus. 

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