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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was previously shown that virus-specific polypeptides made in HEp-2 cells infected with herpes simplex 1 form three groups designated alpha, beta, and gamma whose synthesis is coordinately regulated and sequentially ordered. This report shows that one or more functional alpha polypeptides are necessary to turn on the synthesis of beta and gamma groups, and conversely, one or more polypeptides in the latter groups turn off the synthesis of alpha polypeptides. Specifically, infected cells maintained in medium containing either canavanine, an analogue of arginine, or azetidine-2-carboxylic acid an analogue of proline and hydroxyproline, synthesized alpha polypeptide at rates comparable to maximal rates in untreated infected cells but did not undergo the normal transition to beta and gamma polypeptide synthesis. The transition to gamma polypeptide synthesis and shut-off of synthesis of earlier polypeptide groups proceeded normally if addition of canavanine was delayed until at least 4-5 hr after infection. Addition of canavanine after the onset of beta and gamma polypeptide synthesis, i.e., between 2 and 3.5 hr after infection, resulted in sustained, simultaneous synthesis of all three polypeptide groups, a phenomenon not seen in untreated infected cells. Canavanine-treated infected cells, synthesizing alpha polypeptides, recovered the capacity to make beta and gamma polypeptides after removal of the analogue, but only after a 1-to 2-hr delay compared with infected untreated cells. The data indicate that the on and off controls inherent in the cascade regulation of viral polypeptide synthesis are mediated by one or more polypeptides in each group at transcriptional or post-transcriptional levels.
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PMID:Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides. 16 3

Protein synthesis initiation in reticulocyte lysates is inhibited by heme deficiency, low levels of double-stranded RNA (dsRNA), oxidized glutathione (GSSG), or the purified kinase (HRI) that acts on the alpha polypeptide of eukaryotic initiation factor 2 (eIF-2alpha). The phosphoprotein profiles produced in lysates in response to these various conditions have been monitored directly in lysates after labeling for brief periods with pulses of [gamma-(32)P]ATP. The [(32)P]phosphoprotein profiles were analyzed by electrophoresis in sodium dodecyl sulfate/polyacrylamide slab gels under conditions in which the HRI and eIF-2alpha polypeptides were clearly distinguished. All four modes of inhibition produced a rapid phosphorylation of eIF-2alpha compared to control lysates, which displayed little or no phosphorylation of eIF-2alpha. In heme-deficient lysates, phosphorylation of eIF-2alpha occurred rapidly both before and after the shut-off of protein synthesis; the delayed addition of hemin to these lysates resulted in a decrease in the phosphorylation of eIF-2alpha and the subsequent restoration of protein synthesis. These data suggest that rapid turnover of phosphate occurs at the site(s) of eIF-2alpha phosphorylation. In lysates inhibited by heme deficiency, GSSG, or added HRI, the phosphorylation of eIF-2alpha was accompanied by the rapid in situ phosphorylation of HRI. The inhibition of initiation induced by dsRNA was accompanied by the phosphorylation of eIF-2alpha and a 67,000-dalton polypeptide but not HRI. These observations in situ indicate that (i) the phosphorylation of eIF-2alpha is the critical event in these inhibitions of protein chain initiation, and (ii) the phosphorylation of HRI is associated with its activation in heme deficiency.
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PMID:In situ phosphorylation of the alpha subunit of eukaryotic initiation factor 2 in reticulocyte lysates inhibited by heme deficiency, double-stranded RNA, oxidized glutathione, or the heme-regulated protein kinase. 28 50

An investigation of virus-specific protein synthesis in infectious pancreatic necrosis virus (IPNV)-infected rainbow trout gonad cells was undertaken to find a relationship between the coding capacity of the virus genome (two segments of double-stranded RNA of 2.5 x 10(6) and 2.3 x 10(6) molecular weight) and the sizes and relative amounts of virus-specific proteins. Using polyacrylamide slabgel electrophoresis and autoradiography, eight distinct virus-specific polypeptides were detected in infected, [(35)S]methionine-labeled cells. These proteins may be grouped into three size classes on the basis of molecular weight: (i) large, alpha (90,000); (ii) medium, beta(1) (59,000), beta(2) (58,000), and beta(3) (57,000); and (iii) small, gamma(1) (29,000), gamma(1A) (28,000), gamma(2) (27,000), and gamma(3) (25,000). The combined molecular weight of these polypetides (373,000) is beyond the coding capacity of the virus genome. Purified IPNV contained polypeptides alpha, beta(3), gamma(1), and gamma(1A). Pulse-chase experiments and tryptic peptide map comparisons revealed that only four of the eight intracellular proteins were primary gene products, namely, alpha, beta(1), gamma(1), and beta(2), with a combined molecular weight of 205,000. Of these primary gene products only the alpha polypeptide was found to be stable, whereas the other three underwent intracellular proteolytic cleavage during virus morphogenesis. Polypeptide beta(1) was cleaved to generate beta(2) and beta(3); gamma(1) was trimmed to produce gamma(1A), and the only nonstructural primary gene product, gamma(2), was found to be a precursor of gamma(3). These results suggest that IPNV possesses a unique mechanism to synthesize three size classes of proteins using mRNA transcripts from two high-molecular-weight double-stranded RNA genome segments.
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PMID:Peptide map comparison of infectious pancreatic necrosis virus-specific polypeptides. 56 79

Structural properties of two similar beta-galactosidase fragments were investigated to determine how they influence the fragments' degradation rate in Escherichia coli. Both fragments resulting from a C-terminal nonsense mutation in lacZ, the CSH11 polypeptide and its 90 kDa degradative intermediate, exist predominantly as monomer subunits instead of in the tetrameric form characteristic of the native enzyme. However, both fragments appear to produce trace amounts of dimers and tetramers. The tetramer and higher molecular weight aggregates formed by the wild-type subunit confer greater protection for the enzyme's N-terminal auto-alpha polypeptide than does the monomer state of the beta-galactosidase fragments. The thermally induced aggregation of both beta-galactosidase fragments correlates with their sensitivity to alpha-chymotrypsin. The relatively low thermal stability of the 90 kDa degradative intermediate appears to be the cause of the significant increase in its proteolytic susceptibility at moderately high temperatures.
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PMID:Structural characteristics of an abnormal protein influencing its proteolytic susceptibility. 136 59

The KP6 toxin of Ustilago maydis, encoded by segmented double-stranded (ds) RNA viruses, is lethal to sensitive strains of the same species and related species. The toxin consists of two polypeptides, alpha and beta, synthesized as a single preprotoxin, which are not covalently linked. Neither polypeptide alone is toxic, but killer activity can be restored by in vitro and in vivo complementation. Killer-secreting strains are resistant to the toxin they produce. Resistance is conferred by a single recessive nuclear gene. This study describes a search for cytoplasmic factors that may confer resistance, also referred to as immunity. The approaches used to detect cytoplasmic immunity included transmission of dsRNA and transmission of virus particles to sensitive cells by cytoduction, cytoplasmic mixing in diploids and infection with viruses. An alternative approach was also used to express cloned cDNAs of the KP6 toxin-encoding dsRNA and of the alpha and beta polypeptides. The results indicated that no immunity to KP6 can be detected. While KP6, alpha and beta polypeptides were expressed by resistant cells, neither KP6 nor beta were expressed in sensitive strains. The alpha polypeptide was expressed in sensitive cells, but it did not confer immunity. These results suggest that neither the preprotoxin nor the alpha or beta polypeptides confer immunity and thus beta may be the toxic component of the binary toxin.
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PMID:Immunity and resistance to the KP6 toxin of Ustilago maydis. 162 96

Synthetic mRNAs (i.e. cRNA alpha and cRNA beta) were obtained by cell-free transcription of M13 KS(+) (Bluescript) expression vectors which contained the entire coding region of the alpha or beta subunits of lamb kidney Na,K-ATPase. Translation in reticulocyte lysates of cRNA alpha yielded full length alpha polypeptide, as well as a limited array of immunoprecipitable lower molecular weight products. cRNA beta yielded a single immunoprecipitable full length polypeptide. Association of the alpha polypeptide with the microsomal membranes was obtained only co-translationally. Fifteen to 50% of the membrane-associated alpha subunit was resistant to extraction with alkali. The resistance of a 29-kDa fragment to trypsinolysis indicated that the alpha subunit was inserted into microsomal membranes. In the presence of dog pancreatic microsomes, the beta polypeptide was glycosylated as indicated by the appearance of three higher molecular weight polypeptides that were sensitive to endoglycosidase H and bound to Concanavalin A. The beta subunit was predominantly translocated into the lumen of the endoplasmic reticulum since 90% of the mass of the membrane-associated beta polypeptide was resistant to trypsin (i.e. reduced in size from 40 kDa to 37.5 kDa), and 95% of all of the beta chains were resistant to extraction with alkali. Neither the alpha nor the beta subunits have NH2-terminal leader signal sequences, but both may require the signal recognition receptor for membrane insertion, as evidenced by inhibition of incorporation of both subunits into microsomes pretreated with N-ethylmaleimide. Simultaneous translation of cRNA alpha and cRNA beta did not enhance membrane insertion of either the alpha or beta polypeptide.
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PMID:Cell-free transcription and translation of Na,K-ATPase alpha and beta subunit cDNAs. 169 72

A cDNA from a rat hippocampal cDNA library encodes an isoform of the alpha polypeptide of the gamma-aminobutyric acid (GABA)/benzodiazepine (BZ) receptor. Its deduced amino acid sequence is 96% identical to that of the alpha 2 polypeptide of the bovine GABAA receptor. The polypeptide has features shared by all previously reported GABAA receptor alpha polypeptides and shares 71-76% identity with previously described rat alpha polypeptides. Most of the differences lie in the presumed extracellular and intracellular domains. On Northern blots, the alpha 2 cDNA detects two mRNAs, which are found in cortex, hippocampus, and striatum, brain regions enriched in pharmacologically defined "BZ type II" receptors. Other workers have previously shown that the alpha polypeptides of the GABAA receptor largely determine the BZ binding properties of reconstituted receptors. The distribution of alpha 2 mRNAs in rat brain suggests that the alpha 2 subunit may indeed be involved in the BZ type II receptors.
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PMID:Sequence and regional distribution of the mRNA encoding the alpha 2 polypeptide of rat gamma-aminobutyric acidA receptors. 184 52

The light-harvesting complex I (LHI) of Rhodobacter capsulatus is an oligomer of basic subunits each consisting of the two different pigment-binding polypeptides LHI alpha and LHI beta, encoded by the pufA (LHI alpha) and pufB (LHI beta) genes. Pulse-labeling experiments showed that in the presence of the LHI alpha polypeptide, the LHI beta polypeptide was inserted earlier into the intracytoplasmic membrane than was the LHI alpha polypeptide. Each of the pufA and pufB genes was deleted to test whether the LHI alpha and beta polypeptides, respectively, are inserted into the intracytoplasmic membrane independently of the LHI partner polypeptide. Neither deletion mutant strain formed the LHI antenna, but a functional reaction center complex was present. Pulse-labeling experiments indicated that the LHI beta polypeptide was inserted into the intracytoplasmic membrane with the same kinetics and in the same amounts regardless of whether the LHI alpha polypeptide was present. However, the LHI beta polypeptide did not accumulate in the membrane in the absence of the LHI alpha protein but was degraded linearly within about 12 min. In contrast to the LHI beta protein, only trace amounts of the LHI alpha polypeptide were inserted into or attached to the membrane if the LHI beta polypeptide was not synthesized.
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PMID:Incorporation of light-harvesting complex I alpha and beta polypeptides into the intracytoplasmic membrane of Rhodobacter capsulatus. 188 14

The human gene coding for the 70-kD polypeptide of the complement regulatory component C4b-binding protein (C4BP alpha) spans over 40 kb of DNA and is composed of twelve exons. Upon transcription in liver, or in Hep-G2 cells, this gene produces a single transcript of 2,262 nucleotides, excepting the poly A tail, that presents an unusually long 5' untranslated region (5' UTR) of 223 nucleotides. The C4BP alpha gene is organized as follows: the first exon codes for the first 198 nucleotides of the 5' UTR. It is separated by a large intron from the second exon including the remaining of the 5' UTR and the coding region for the signal peptide. Each of the eight 60-amino acid repeats (short consensus repeats [SCRs]) that compose the C4BP alpha polypeptide chain is encoded by a single exon, except for the second SCR, which is split in two exons. At the 3' end of the C4BP alpha gene, the twelfth exon codes for the COOH-terminal 57 amino acids of the mature protein, which have no similarities to the SCRs, and the 245 nucleotides of the 3' UTR. Examination of the nucleotide sequence of the first exon revealed an interesting characteristic, strongly suggesting that this exon may specify a functional domain of the C4BP alpha transcript. It includes two in-phase ATG codons, in a different frame respect to that coding the C4BP alpha polypeptide, followed by an in-frame termination codon, also within the first exon. Comparison between mouse and human C4BP alpha transcripts indicates conservation of this structure within the 5' UTR. C4BP is expressed in the liver and is an acute phase protein. A computer search of the genomic sequences upstream the transcription start site demonstrates the presence of potential cis-acting regulatory elements similar to those found in the promoters of other liver-expressed and/or acute phase genes.
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PMID:Structure of the gene coding for the alpha polypeptide chain of the human complement component C4b-binding protein. 202 20

Three distinct gene products, the alpha and beta chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. We have analyzed the molecular basis of this disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ib alpha but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ib alpha, which by lacking half of the sequence on the carboxyl-terminal side, including the trans-membrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ib alpha allele. Nonsense mutation and truncated GP Ib alpha polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ib alpha alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome.
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PMID:Nonsense mutation in the glycoprotein Ib alpha coding sequence associated with Bernard-Soulier syndrome. 230 62


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