Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the mode of action of norakin against influenza A virus we sequenced the hemagglutinin gene of 11 norakin-resistant mutants. Resistance was coupled with 1-3 amino acid exchanges. The majority of mutations was localized in the HA2 polypeptide and was mostly associated with changes in charge or polarity of the amino acids. The amino acid substitutions are discussed in the context of the 3D structure of X31 hemagglutinin considered to be representative of the influenza hemagglutinins. Most of the mutations appear to destabilize the pH 7.0 structure by distorting or destroying hydrogen bonds as well as salt-bridges which are responsible for intra- and intersubunit contacts, while others destabilize the location of the fusion peptide, facilitating conformational changes in the presence of the inhibitor.
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PMID:Mapping mutations in influenza A virus resistant to norakin. 236 87

Sequence analysis of the neuraminidase (NA) genes of influenza virus X-7(F1) and of 12 variants selected with monoclonal antibodies has been used to define in physical terms the antigenic structure of this NA, which was operationally established by R. G. Webster, L. E. Brown, and W. G. Laver (1984, Virology 135, 30-42). X-7(F1) is a reassortant virus containing the NA of the early Asian (H2N2) isolate A/RI/5+/57, and the results of antigenic and sequence analysis of X-7(F1) and of variants selected with monoclonal antibodies have been combined with a similar analysis of the A/Tokyo/3/67 NA (H2N2, M. R. Lentz, G. M. Air, W. G. Laver, and R. G. Webster (1984), Virology 135, 257-265) to obtain a model of antibody binding to N2 NAs. The selection process was biased, however, since only those monoclonal antibodies which inhibited NA activity could be used to select variants. Most of the changes in the variants selected with monoclonal antibodies occur in those parts of the polypeptide chain which encircle the enzyme active site pocket in the three-dimensional structure (P. M. Colman, J. N. Varghese, and W. G. Laver (1983), Nature (London) 303, 41-44). The results suggest that in general the antibody binds to a site on the NA which includes those amino acid side chains which are altered in monoclonal variants. There are, however, several aspects of the antigen-antibody interaction which are not easily explained, and which will probably only be fully elucidated by X-ray crystallographic analysis of NA-antibody complexes.
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PMID:Location of antigenic sites on the three-dimensional structure of the influenza N2 virus neuraminidase. 241 Oct 49

The biological function of a cold-adapted (ca) mutation residing on the PB2 gene of an influenza A/Ann Arbor/6/60 (A/AA/6/60) ca variant virus in the viral replication cycle at 25 degrees C was studied. The viral polypeptide synthesis of A/AA/6/60 ca variant at 25 degrees C was evident approximately 6 hours earlier than the wild type (wt) virus and yielded twice as many products. The quantitative analysis of viral complementary RNA (cRNA), synthesized in the presence of cycloheximide, revealed that A/AA/6/60 ca variant and a single gene reassortant that contains only the PB2 gene of the ca variant with remaining genes of the wt virus produced equal amount of cRNA at 25 degrees and 33 degrees C, which was an amount approximately four fold greater than the wt virus' cRNA synthesized at 25 degrees C. These results strongly suggest that the ca mutation residing on the PB2 gene of A/AA/6/60 ca variant affects the messenger RNA synthesis at 25 degrees C in the primary transcription.
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PMID:Biological characteristics of a cold-adapted influenza A virus mutation residing on a polymerase gene. 242 Mar 13

A fine specificity analysis of influenza hemagglutinin-specific IAk-restricted T cell clones using natural virus variants of the H3N2 subtype, monoclonal antibody-selected variants and a synthetic peptide corresponding to a variable region of the HA1 polypeptide has provided insight on the structural basis for T cell recognition. A glycine to arginine substitution at HA1 135 abrogates recognition by a panel of T cell clones which, according to their reactivity for natural virus variants, have different antigenic specificities: three clones recognize a synthetic peptide (HA1 residues 118-138) but fail to recognize the monoclonal antibody-selected mutant (Gly135/Arg). There is no correlation, however, between differences in T cell specificity for the natural virus variants and HA1 amino acid sequences in this region. Two further clones have a reduced proliferative response to mutant recognize a completely different spectrum of natural variants, and only one of these clones recognizes the synthetic peptide. We speculate that influenza hemagglutinin employs a common strategy during antigenic drift to evade antibody recognition and effective processing/presentation to subtype-specific T cell clones.
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PMID:A single amino acid substitution in influenza hemagglutinin abrogates recognition by monoclonal antibody and a spectrum of subtype-specific L3T4+ T cell clones. 243 37

A total of 14 I-Ad-restricted helper T-cell clones specific for the hemagglutinin (HA) molecule of influenza virus were isolated from spleens of BALB/c or (BALB/c X C57BL/10)F1 mice immunized with the H3 subtype influenza virus A/Memphis/71 (Mem 71) and from lymph nodes of BALB/c mice primed with purified HA. The specificity of these T-cell clones was assessed in proliferation assays by reactivity with naturally occurring strains of viruses that arose by antigenic drift and contain known amino acid sequence changes in HA and with a panel of monoclonal antibody (MAb)-selected mutants of Mem 71 with single amino acid substitutions in HA. The HA genes of those mutant viruses that failed to stimulate one or more of the T-cell clones were sequenced. The clones could be allocated to at least four groups, each group having a distinct pattern of reactivity with the panel of natural field strains. The epitopes recognized by the four groups of clones were found, by reactivity with MAb-selected mutants, to be in very close proximity to one another and probably overlapping. All of the distinct epitopes recognized by the T-cell clones were adversely affected by a single amino acid substitution, either at residue 60 or at residue 63 in the HA1 polypeptide chain, within the region known from antibody-binding studies as site E. Some, but not all, of the epitopes may be influenced by the addition of a carbohydrate side chain to the HA of a particular MAb-selected mutant and certain field strains containing an Asp----Asn substitution at residue 63. Site E is therefore a major site of H-2d helper T-cell recognition on the H3 HA.
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PMID:Distinct epitopes recognized by I-Ad-restricted T-cell clones within antigenic site E on influenza virus hemagglutinin. 244 16

In our previous study, seven monoclonal antibodies specific for influenza C virus glycoprotein (gp88) were prepared and tentatively classified into two groups: group A (J14, J9, Q5, K16) has neutralization activity whereas group B (S16, J6, J15) does not. These antibodies were used to analyse the antigenic structure of gp88 and to examine the effect of glycosylation on the antigenicity of the glycoprotein. Operational analysis with a panel of antigenic variants selected with each of the group A antibodies identified two non-overlapping antigenic sites on the gp88 molecules, site A-1 recognized by J14, J9 and Q5 and site A-2 by K16. Sites A-1 and A-2 were shown, however, to be topographically overlapping by competitive binding assays. Competitive binding analysis with group B antibodies identified two additional non-over-lapping antigenic sites, site B-1 recognized by S16 and site B-2 by J6 and J15. It was found in radioimmunoprecipitation experiments that antibodies to sites B-1 and B-2 were reactive not only with gp88 but with its non-glycosylated form (T76) synthesized in the presence of tunicamycin. Antibodies to sites A-1 and A-2, in contrast, immunoprecipitated the T76 polypeptide in only trace amounts or not at all. Additionally, Western blot analysis showed that denatured gp88 blotted on nitrocellulose was reactive with antibodies to sites B-1 and B-2 but not with those to sites A-1 and A-2. These observations suggest that glycosylation of gp88 selectively influences the integrity of antigenic sites A-1 and A-2 which are composed of conformation-dependent epitopes.
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PMID:Operational and topological analyses of antigenic sites on influenza C virus glycoprotein and their dependence on glycosylation. 245 Sep 65

The rotavirus glycoprotein VP7 has a cleavable signal peptide and is normally resident as an integral membrane protein in the ER of infected cells. A gene was constructed in which the VP7 H2 signal peptide was replaced by one from influenza hemagglutinin. COS cells transfected with this gene produced VP7 with the correct amino terminus, but the protein was rapidly secreted. Uncleaved VP7 from either precursor was not detected in cells after brief pulse-labeling, suggesting that the signal peptide was not acting as a temporary anchor; rather, it exerted its effect despite rapid cleavage. By splicing the H2 signal peptide onto another reporter protein, the malaria S-antigen, we demonstrated that H2 was necessary, but not itself sufficient, for targeting and retention. We propose that an interaction between the cleaved signal peptide and other downstream sequences in VP7 is required for retention of this protein in the ER as an integral membrane polypeptide.
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PMID:The signal peptide of the rotavirus glycoprotein VP7 is essential for its retention in the ER as an integral membrane protein. 253 41

The influenza A virus M2 polypeptide is a small integral membrane protein that does not contain a cleaved signal sequence, but is unusual in that it assumes the membrane orientation of a class I integral membrane protein with an NH2-terminal ectodomain and a COOH-terminal cytoplasmic tail. To determine the domains of M2 involved in specifying membrane orientation, hybrid genes were constructed and expressed in which regions of the M2 protein were linked to portions of the paramyxovirus HN and SH proteins, two class II integral membrane proteins that adopt the opposite orientation in membranes from M2. A hybrid protein (MgMH) consisting of the M2 NH2-terminal and membrane-spanning domains linked precisely to the HN COOH-terminal ectodomain was found in cells in two forms: integrated into membranes in the M2 topology or completely translocated across the endoplasmic reticulum membrane and ultimately secreted from the cell. The finding of a soluble form suggested that in this hybrid protein the anchor function of the M2 signal/anchor domain can be overridden. A second hybrid which contained the M2 NH2 terminus linked to the HN signal anchor and ectodomain (MgHH) was found in both the M2 and the HN orientation, suggesting that the M2 NH2 terminus was capable of reversing the topology of a class II membrane protein. The exchange of the M2 signal/anchor domain with that of SH resulted in a hybrid protein which assumed only the M2 topology. Thus, all these data suggest that the NH2-terminal 24 residues to M2 are important for directing the unusual membrane topology of the M2 protein. These data are discussed in relationship to the loop model for insertion of proteins into membranes and the role of charged residues as a factor in determining orientation.
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PMID:Transposition of domains between the M2 and HN viral membrane proteins results in polypeptides which can adopt more than one membrane orientation. 255 41

Recombinant plasmids were constructed in which genes coding for either the entire or the signal-minus (amino acid residues 2-17 deleted) hemagglutinin (HA) of WSN influenza virus were placed under the control of the alcohol dehydrogenase I gene promoter of Saccharomyces cerevisiae. Both recombinant plasmids were shown to direct the synthesis of HA-specific polypeptides that were detected by immunoprecipitation with antiviral antibodies. The complete HA produced in yeast had an approximate Mr of 70,000 and was glycosylated, as determined by the endoglycosidase H sensitivity, and was bound to membrane. Therefore, the complete HA polypeptide possessing the signal sequence probably traversed the yeast secretory pathways. Signal-minus HA, on the other hand, had a lower molecular weight and was nonglycosylated. The specific binding of yeast HA with antiviral antibodies could be competitively inhibited by influenza viral HA, demonstrating that the HA produced in yeast contained antigenic determinants of the native viral HA.
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PMID:Influenza viral (A/WSN/33) hemagglutinin is expressed and glycosylated in the yeast Saccharomyces cerevisiae. 258 Mar 4

The complete nucleotide sequence of the large (L) genome segment of Bunyamwera virus has been determined from overlapping cDNA clones. The segment is 6875 nucleotides long and has a base composition of 29.8% A, 17.9% C, 15.4% G, and 36.9% U. Eighteen of the terminal 19 nucleotides at the 3' and 5' ends are complementary. In the viral-complementary (+ sense) RNA there is a single long open reading frame (ORF) from AUG at bases 51-53 to a UAG stop codon at bases 6765-6767; this ORF encodes a polypeptide of 2238 amino acids (MW 259,000), corresponding to the L protein which has been mapped to the L RNA segment by analysis of reassortants of Bunyamwera, Batai, and Maguari viruses. The amino-terminal 46 amino acids of the L protein show strong homology (63% identity) with the amino-termini of ORFs predicted from limited sequence analysis of the L segments of La Crosse and snowshoe hare bunyaviruses. Comparison with the polymerase proteins encoded by other negative-strand viruses showed weak homology with part of the influenza virus PB1 protein, but no homology was detected with the other influenza virus polymerase proteins nor with the L proteins of arenaviruses, paramyxoviruses, and rhabdoviruses. At the 5' end of genomic (- sense) RNA there is an AUG-initiated ORF potentially encoding a protein of 14,700; the significance of this ORF is unknown at present.
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PMID:Nucleotide sequence analysis of the large (L) genomic RNA segment of Bunyamwera virus, the prototype of the family Bunyaviridae. 259 23


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