Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of glycosylation in intracellular transport and cell surface expression of the vesicular stomatitis virus glycoprotein (G) in cells expressing G protein from cloned cDNA. The individual contributions of the two asparagine-linked glycans of G protein to cell surface expression were assessed by site-directed mutagenesis of the coding sequence to eliminate one or the other or both of the glycosylation sites. One oligosaccharide at either position was sufficient for cell surface expression of G protein in transfected cells, and the rates of oligosaccharide processing were similar to the rate observed for wild-type protein. However, the nonglycosylated G protein synthesized when both glycosylation sites were eliminated did not reach the cell surface. This protein did appear to reach a Golgi-like region, as determined by indirect immunofluorescence microscopy, however, and was modified with palmitic acid. It was also apparently not subject to increased proteolytic breakdown.
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PMID:A single N-linked oligosaccharide at either of the two normal sites is sufficient for transport of vesicular stomatitis virus G protein to the cell surface. 301 99

We have examined the effects of deoxynojirimycin and castanospermine, compounds known to inhibit the removal of glucose from high mannose asparagine-linked oligosaccharides, on the formation of Sindbis virus. These drugs inhibited virion formation in baby hamster kidney (BHK) cells, 15B - the CHO cell line that lacks GlcNAc transferase activity, and chicken embryo fibroblasts, although our results with the latter cells were variable. We analyzed the [3H]mannose-labeled oligosaccharides from Sindbis virus infected 15B cells. Those from control cells were predominantly GlcNAc2Man5. Oligosaccharides from the treated cells were larger than the Man5 species and as expected, were partially resistant to alpha-mannosidase. The growth of Sindbis virus was inhibited to a much greater extent at 37 degrees C than at 30 degrees C in BHK cells treated with either deoxynojirimycin or castanospermine. Both of these compounds also inhibited the proteolytic cleavage of the viral glycoprotein precursor, PE2, to the virion glycoprotein, E2, but did not prevent the migration of the glycoprotein to the cell surface. These results, taken together with our earlier studies with vesicular stomatitis virus (Schlesinger et al., 1984) provide strong evidence that the removal of glucose residues during the processing of asparagine-linked oligosaccharides is critical for some proteins to achieve a functional conformation.
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PMID:The effects of inhibitors of glucosidase I on the formation of Sindbis virus. 315 36

High-molecular-weight, asparagine-linked glycopeptides--the lactosaminoglycans--are the major class of protein-bound carbohydrates synthesized by F9 cells; these cells synthesize only minor amounts of smaller glycopeptides. In contrast, F9ACC19, an endodermal cell line derived from F9 cells, synthesizes only minor amounts of lactosaminoglycans and a high proportion of smaller glycopeptides. Biochemical analysis of the small glycopeptides from F9ACC19 cells revealed that they are larger, bind less efficiently to concanavalin-A Sepharose and contain more sialic acid than their counterparts from F9 cells. Both cell types contain a small proportion of high-mannose glycopeptides. When synthesized by F9ACC19 cells, the glycopeptides of vesicular stomatitis virus show a high level of sialylation as compared to those synthesized by F9 cells, where few or no sialic-acid residues are present; this shows that the differences observed in total glycopeptides reflect differences in the glycosylation machinery of the cells. Consistent with this observation, sialyltransferase activity in vitro using a variety of acceptors was found to be markedly higher in F9ACC19 than in F9 cells, while galactosyltransferase activity was reduced several fold in F9ACC19 cells. These data support the hypothesis that the increased sialyltransferase activity in endodermal differentiated F9ACC19 cells may block the terminal galactose residue of glycopeptides, thereby inhibiting the synthesis of lactosaminoglycans in these cells.
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PMID:Increased sialylation of complex glycopeptides during differentiation of mouse embryonal carcinoma cells. 392 74

Earlier, we reported a 30-200-fold reduction in the yield of infectious vesicular stomatitis virus (VSV) released from L cells treated with 10-30 reference units ml-1 of interferon (IFN); however, in these cultures virus particle production, as measured by VSV particle-associated viral RNA, virus nucleocapsid protein and viral transcriptase, was inhibited less than 10-fold. There was biochemical and morphological evidence of a significant reduction in glycoprotein (G) and membrane protein (M) of VSV particles released from IFN-treated cells. We compare here the effects of tunicamycin (TM) and IFN in L cells. Treatment with TM or IFN reduced the production of infectious VSV particles, decreased the amount of G and M proteins in VSV released from treated cells, and inhibited an early step in the formation of asparagine-linked oligosaccharide chains, the incorporation by membrane preparations from treated cells of N-acetylglucosamine into glycolipids with the properties of dolichol derivatives.
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PMID:Interferon treatment inhibits glycosylation of a viral protein. 615 39

The envelope glycoprotein, G, of vesicular stomatitis virus (VSV) is initially glycosylated by the en bloc transfer of Glc3Man9GlcNAc2 oligosaccharides to 2 specific asparagine residues in the nascent polypeptide chain. We carried out in vivo and in vitro studies to determine whether the size of the oligosaccharide chains on two related but different G proteins can affect their ability to fold correctly. For the in vivo studies we used a mutant lymphoma cell line, Thy-1-e, which transfers the truncated oligosaccharide, Glc3Man5GlcNAc2, to nascent polypeptides. The growth of VSV in these cells was temperature-sensitive compared to that in parental Thy-1+ cells, and VSV (San Juan) was more affected than VSV (Orsay). These results are congruous with our previous observation that in the absence of glycosylation virus assembly is temperature-sensitive and VSV (San Juan) is inhibited more than VSV (Orsay). To examine the effect of oligosaccharide size on the properties of the G protein in vitro we treated G proteins containing either Man8GlcNAc2 or Man5GlcNAc2 oligosaccharide chains with guanidine hydrochloride and measured their ability to refold using an in vitro aggregation assay. The San Juan G protein with Man5GlcNAc2 oligosaccharides aggregated at 40 degrees C but not at 30 degrees C. The Orsay G protein with Man5GlcNAc2 oligosaccharides and both proteins containing Man8GlcNAc2 oligosaccharides did not aggregate at either temperature. We conclude that the size of the oligosaccharides present on the folding G protein can be crucial in attaining a proper conformation, and the extent of their effect depends on the primary structure of the polypeptide.
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PMID:The effect of oligosaccharide chains of different sizes on the maturation and physical properties of the G protein of vesicular stomatitis virus. 625 53

The complete nucleotide sequences of the vesicular stomatitis virus mRNA's encoding the glycoprotein (G) and the matrix protein (M) have been determined from cDNA clones that contain the complete coding sequences from each mRNA. The G protein mRNA is 1,665 nucleotides long, excluding polyadenylic acid, and encodes a protein of 511 amino acids including a signal peptide of 16 amino acids. G protein contains two large hydrophobic domains, one in the signal peptide and the other in the transmembrane segment near the COOH terminus. Two sites of glycosylation are predicted at amino acid residues 178 and 335. The close correspondence of the positions of these sites with the reported timing of the addition of the two oligosaccharides during synthesis of G suggests that glycosylation occurs as soon as the appropriate asparagine residues traverse the membrane of the rough endoplasmic reticulum. The mRNA encoding the vesicular stomatitis virus M protein is 831 nucleotides long, excluding polyadenylic acid, and encodes a protein of 229 amino acids. The predicted M protein sequence does not contain any long hydrophobic or nonpolar domains that might promote membrane association. The protein is rich in basic amino acids and contains a highly basic amino terminal domain. Details of construction of the nearly full-length cDNA clones are presented.
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PMID:Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus G and M proteins determined from cDNA clones containing the complete coding regions. 626 40

K-562 cells, which express foetal erythroglycan, are shown to synthesize the lipid-linked oligosaccharide intermediates commonly found in tissues and cultured fibroblasts. The addition of tunicamycin, which blocks the formation of these intermediates and thus of asparagine-linked oligosaccharides, inhibits the synthesis of erythroglycan (Mr 7000-11 000). Vesicular-stomatitis-virus infection of K-562 cells results in the glycosylation of the G-protein with the transferrin-type oligosaccharide (Mr 3000), but not with the larger erythroglycan. These results suggest that, in K-562 cells, the early stages of erythroglycan biosynthesis are the same as those of the transferrin-type oligosaccharides. However, maturation of the oligosaccharide is influenced by protein structure such that erythroglycan is only expressed on specific glycoproteins.
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PMID:Erythroglycan biosynthesis in K-562 cells. Inhibition of synthesis by tunicamycin and lack of attachment to the G-protein of vesicular-stomatitis virus. 627 7

A method is presented for separation of tryptic glycopeptides-containing oligosaccharides of the N-asparagine-linked type. High performance liquid chromatography (HPLC) of glycopeptides on a C18 reverse-phase system eluted with a gradient of 0%-50% acetonitrile in 0.1 M NaPO4 pH 2.2 resolves the two major glycosylation sites from the envelope glycoprotein (G) of vesicular stomatitis virus. Glycopeptides containing N-linked oligosaccharides of the complex type coelute with those containing N-linked oligosaccharides of the neutral, high mannose type, indicating that separation is based upon peptide rather than carbohydrate composition. The contribution of the carbohydrate component to glycopeptide elution, as determined by cleavage of the high mannose oligosaccharides with endo-beta-Nacetylglucosaminidase H, is that of a significant, but minor, decrease in peptide retention time. Comparison of the tryptic glycopeptide profiles of G isolated from both wild type and mutant strains of VSV illustrates the rapid, reproducible, and quantitative nature of the technique. Through HPLC analysis of appropriately treated glycopeptides, it is possible to explore both the nature and extent of glycosylation at individual sites in glycoproteins in a single step.
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PMID:Separation of glycopeptides by high performance liquid chromatography. 627 84

The asparagine-linked oligosaccharides of the G protein of the Hazelhurst subtype of the New Jersey serotype of vesicular stomatitis virus (VSV) have been compared with the oligosaccharides from the G protein of the well-characterized Indiana serotype of VSV, with baby hamster kidney cells in monolayer culture as the host for both viruses. [3H]Glucosamine- and [3H]mannose-labeled glycopeptides from the G protein of purified virus were analyzed by the combined techniques of endo-beta-N-acetylglucosaminidase H (ENDO-H) digestion, concanavalin A and lentil lectin affinity chromatography, and Bio-Gel P-4 chromatography. Although almost all of the Indiana G protein oligosaccharides were acidic-type structures, as expected from previous studies; the Hazelhurst G protein contained a mixture of acidic-type, hybrid-type containing sialic acid, and neutral-type (predominantly Man5-6GlcNAc2-Asn) structures. The vast majority of acidic-type oligosaccharides from both the Hazelhurst and Indiana G proteins were diantennary structures, with less than half containing fucose linked to the innermost N-acetylglucosamine. Additional analysis of the Hazelhurst G protein by ENDO-H digestion and gel electrophoresis suggested that some of the mature G polypeptides contained acidic-type structures at both glycosylation sites, whereas the remainder contained an ENDO-H-resistant, acidic-type structure at one site and an ENDO-H-sensitive, hybrid- or neutral-type structure at the other site.
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PMID:Unusual heterogeneity in the glycosylation of the G protein of the hazelhurst strain of vesicular stomatitis virus. 631 2

We have studied the effects of inhibiting the initial steps in processing of asparagine-linked oligosaccharides on the formation of vesicular stomatitis virus (VSV). Our data show that conditions which prevent the removal of glucose can block the growth of this virus. Our conclusion that inhibition of VSV synthesis is due specifically to an effect on the ability of the virus glycoprotein, G, to mature to a correct functional conformation is based on the following observations: (i) two drugs, deoxynojirimycin and castanospermine , both of which selectively inhibit the processing glucosidases, affected virus growth; (ii) only one of the two strains (San Juan and Orsay ) of VSV tested was affected and that strain, VSV(San Juan), is known to have a G protein highly sensitive to alterations in oligosaccharide structure; (iii) the effect was to make the formation of VSV(San Juan) temperature-sensitive, a result previously observed with alterations in the oligosaccharides on G protein; (iv) a cell variant missing glucosidase II activity also became temperature-sensitive in its ability to produce VSV(San Juan) but not VSV( Orsay ). Although inhibition of glucosidase activity by 1- deoxynojirimycin caused a 10-fold drop in virion formation, transport of G protein to the plasma membrane was not altered. The growth of VSV(San Juan) at 40 degrees C was not affected when subsequent steps in the processing pathway were blocked. These data indicate that by the time the glucose residues are removed G has attained a stable conformation.
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PMID:The formation of vesicular stomatitis virus (San Juan strain) becomes temperature-sensitive when glucose residues are retained on the oligosaccharides of the glycoprotein. 633 65


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