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)

Influenza virus hemagglutinin (HA) subtype H7 expressed from a baculovirus vector in insect cells requires cysteine residues for palmitoylation. Mutant HA devoid of fatty acids shows hemagglutinating and hemolytic activities almost identical to those of the acylated wild-type HA (wt). Using a membrane mixing assay (R18), neither the kinetics nor the pH dependence of fusion induced by wt or mutant HA was significantly different from virus-induced fusion. HA-induced fusion of insect cells with human erythrocyte ghosts could also be demonstrated by a cytoplasmic content mixing assay. Both species of recombinant HA induced the flow of lucifer yellow from preloaded ghosts into the cytoplasm of HA-bearing cells. This indicates that membrane fusion mediated by wild-type and fatty-acid-free HA includes both leaflets of the lipid bilayers. Hydroxylamine treatment of wt HA (H7) and fatty-acid-free mutant HA present in lysates of insect cells led to the complete inhibition of hemolytic activity. Deacylation of spike proteins by NH2OH treatment of virus particles resulted in a block of hemolytic activity in influenza virus subtypes H7 and H10 as well as of that in the togaviruses Semliki Forest and Sindbis virus. However, the same treatment did not affect subtypes H2 and H3 or two vesicular stomatitis virus serotypes. With such a differential effect whether or not fatty acids are present in the spike proteins of the different virus particles, hydroxylamine must have other effects than just deacylation, and therefore seems unsuitable for the study of the biological functions of acylproteins.
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PMID:Assessment of fusogenic properties of influenza virus hemagglutinin deacylated by site-directed mutagenesis and hydroxylamine treatment. 779 71

The spike glycoprotein G of vesicular stomatitis virus (VSV) induces membrane fusion at low pH. We used linker insertion mutagenesis to characterize the domain(s) of G glycoprotein involved in low-pH-induced membrane fusion. Two or three amino acids were inserted in frame into various positions in the extracellular domain of G, and 14 mutants were isolated. All of the mutants expressed fully glycosylated proteins in COS cells. However, only seven mutant G glycoproteins were transported to the cell surface. Two of these mutants, D1 and A6, showed wild-type fusogenic properties. The mutant A2 had a temperature-sensitive defect in the transport of the mutant G glycoprotein to the cell surface. The other four mutants, H2, H5, H10, and A4, although present in cell surface, failed to induce cell fusion when cells expressing these mutant glycoproteins were exposed to acidic pH. These four mutant G proteins could form trimers, indicating that the defect in fusion was not due to defective oligomerization. One of these mutations, H2, is within a region of conserved, uncharged amino acids that has been proposed as a possible fusogenic sequence. The mutation in H5 was about 70 amino acids downstream of the mutation in H2, while mutations in H10 and A4 were about 300 amino acids downstream of the mutation in H2. Conserved sequences were also noted in the H10 and A4 segment. The results suggest that in the case of VSV G glycoprotein, the fusogenic activity may involve several spatially separated regions in the extracellular domain of the protein.
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PMID:Mutational analysis of the vesicular stomatitis virus glycoprotein G for membrane fusion domains. 838 17

Site-directed mutagenesis of specific amino acids within a conserved amino-terminal region (H2) and a conserved carboxyl-terminal region (H10/A4) of the fusion protein G of vesicular stomatitis virus have previously identified these two segments as an internal fusion peptide and a region influencing low-pH induced conformational change, respectively. Here, we combined a number of the substitution mutants in the H2 and H10/A4 regions to produce a series of double-site mutants and determined the effect of these mutations on membrane fusion activity at acid pH and on pH-dependent conformational change. The results show that most of the double-site mutants have decreased cell-cell fusion activity and that the effects appeared to be additive in terms of inhibition of fusion, except for one mutant, which appeared to be a revertant. The double-site mutants also had pH optima for fusion that were lower than those observed with wild-type G but same as the pH optima for the parent fusion peptide (H2) mutants. The results suggest that although the H2 and H10/A4 sites may affect membrane fusion independently, a possible interaction between these two sites cannot be ruled out.
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PMID:Effects of double-site mutations of vesicular stomatitis virus glycoprotein G on membrane fusion activity. 1008 32