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)

Toward elucidating molecular details of virus-induced membrane fusion, we have studied the low pH-triggered interaction of the bromelain-solubilized ectodomain of influenza hemagglutinin with liposomes. Polypeptide segments which insert into the apolar phase of the lipid bilayer were first labeled specifically using either of the two membrane-restricted carbene-generating reagents, 3-(trifluoromethyl)-3-([125I]iodophenyl)diazirine and 1-palmitoyl-2-[11-[4-[3-(trifluoromethyl)diazirinyl]phenyl] undecanoyl]-sn-glycero-3-phosphorylcholine, and were then identified on the basis of cyanogen bromide and 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine-skatole fragment analysis and Edman degradations. Here, we demonstrate that the hydrophobic interaction is mediated solely by the so-called "fusion peptide" which corresponds to the NH2-terminal segment of the BHA2 subunit of nature influenza hemagglutinin. Predominant sites of labeling within that segment were Phe-3, Ile-6, Phe-9, Trp-14, Met-17, and Trp-21. The average 3-4 residue spacing between consecutive labeled amino acid side chains suggests a helical structure of that segment with an amphiphilic character.
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PMID:Hydrophobic binding of the ectodomain of influenza hemagglutinin to membranes occurs through the "fusion peptide". 270 99

To understand the determinants of influenza virus evolution, phylogenetic relationships were determined for nine hemagglutinin (HA) genes of the H4 subtype. These genes belong to a set of viruses isolated from several avian and mammalian species from various geographic locations around the world between 1956 and 1985. We found that the HA gene of the H4 subtype is 1738 nucleotides in length and is predicted to encode a polypeptide of 564 amino acids. The connecting peptide, which is removed from the precursor polypeptide by peptidases to yield the mature HA1 and HA2 polypeptides, contains only one basic amino acid. This type of connecting peptide is a feature of all avian avirulent HAs. On the basis of pairwise nucleotide sequence homology comparisons the genes can be segregated into two groups: influenza virus genes isolated in North America and those isolated from other parts of the world. A high degree of homology exists between pairs of genes from viruses of similar geographic origin. The nucleotide sequences within a group differ by 1.5 to 10.6%; in contrast, between groups the differences range from 15.8 to 19.4%. An evolutionary tree for the nine sequences suggests that North American isolates have diverged extensively from those circulating in other parts of the world. Geographic barriers which determine flyway outlay may prevent the gene pools from extensive mixing. The lack of correlation between date of isolation and evolutionary distance suggests that different H4 HA genes cocirculate in a fashion similar to avian H3 HA genes (H. Kida et al., 1987, Virology 159, 109-119) and influenza C genes (D. Buonagurio et al., 1985, Virology 146, 221-232) implying the absence of selective pressure by antibody that would give a significant advantage to antigenic variants. In contrast to avian influenza virus genes, human influenza virus genes evolve rapidly under the selective pressure of antibody.
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PMID:Distinct lineages of influenza virus H4 hemagglutinin genes in different regions of the world. 270 4

Amantadine has been accepted for both the treatment and prophylaxis of influenza A virus infections. Although amantadine-resistant mutants have been shown to be readily generated both in the laboratory and in children treated with rimantadine, little is known about their biologic properties, such as genetic stability, transmissibility, or pathogenicity, compared with the parental virus. This study examined these properties using an avian influenza virus, A/chicken/Pennsylvania/1370/83 (H5N2). Variants that were amantadine-resistant, virulent, and capable of competing with wild-type virus for transmission to susceptible hosts in the absence of the drug were selected. These amantadine-resistant variants were also genetically stable, showing no reversion to wild-type after six passages in birds over a period of greater than 20 d. Thus, these virus variants had no detectable biologic impairment. The mutations conferring drug resistance were in the M2 polypeptide and were identical to mutations previously described in human amantadine-resistant virus. These results suggest that resistant mutants may have the potential to threaten the effective use of amantadine and rimantadine for the control of epidemic influenza.
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PMID:Biologic potential of amantadine-resistant influenza A virus in an avian model. 272 53

A temperature sensitive mutant, ts C47, derived from A/FPV/Rostock/34 and with a ts mutation in RNA segment 8, fails to form plaques in MDCK cells. From data obtained with reassortant viruses using the human influenza isolate A/FM/1/47 it was apparent that more than one mutation contributed to the temperature-sensitive (ts) and host range (hr) phenotypes of ts C47, and the phenotype of reassortants containing RNA segment 1 from A/FM/1/47 indicated that this segment was involved. A single nucleotide substitution at nucleotide 1961, resulting in valine instead of methionine in the predicted amino acid sequence of polypeptide PB2, was found in RNA segment 1 of ts C47, but this mutation did not segregate with the attenuated phenotype on gene reassortment. The following conclusions are drawn: (a) that ts C47 has at least two mutations in addition to that already known to exist in RNA segment 8, one of which (that in RNA segment 1) does not contribute to the observed ts hr phenotypes and (b) that the hr phenotype can be suppressed by substitution of RNA segment 1 by that of another strain.
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PMID:The role of RNA segment 1 in an in vitro host restriction occurring in an avian influenza virus mutant. 272 18

The influenza virus A/Victoria/3/75 (H3N2) polymerase genes encoding PB1, PB2 and PA have been cloned by cDNA synthesis and insertion into bacterial vectors. The complete sequence for each polymerase gene has been obtained from random M13 subclones and compared to other influenza virus polymerase genes. A total of 45, 74 and 78 nucleotide changes were fixed in the period 1968-1975, corresponding to 10, 12 and 9 amino acid changes, for PB1, PB2 and PA genes, respectively. The amino acid sequence of PB1 polypeptide contains motifs found in a series of positive- and negative-RNA virus polymerase genes and that of PA polypeptide share invariant residues common to DNA and presumptive RNA helicases.
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PMID:Molecular cloning and sequencing of influenza virus A/Victoria/3/75 polymerase genes: sequence evolution and prediction of possible functional domains. 277 94

The contribution of viral infectivity to the expression of MHC class II-restricted T cell determinants was studied. A murine I-Ed-restricted T cell hybridoma recognizing the neuraminidase (NA) glycoprotein of influenza PR8 virus was stimulated strongly by infectious virus but failed to recognize antigen introduced on noninfectious virions. Recognition correlated with the de novo synthesis of viral NA within infected APC. The effectiveness of infectious virus did not depend strictly upon the amount of NA present in cultures, since high NA concentrations could be achieved by addition of nonreplicative virus without being stimulatory for NA-specific T cells. Recognition of a determinant generated only when synthesized in murine host cells was ruled out, since, in high concentration, NA isolated from purified egg-grown virions, even if reduced and alkylated, was recognized by the T hybridoma clone. Isolated NA was recognized when added to pre-fixed APC, suggesting that this form of antigen was able to bypass the usual processing pathway of exogenous proteins. Data suggest that endogenously synthesized antigen may contribute most significantly to presentation of labile T cell determinants. In addition to NA, recognition of an I-Ed-restricted determinant of the influenza hemagglutinin (HA) molecule, shown previously to have a relatively short half-life on APC surfaces, was enhanced greatly by infectious virus. In contrast, T cell recognition of a more stably expressed I-Ed-restricted site of the same HA polypeptide was only marginally improved on infected APC.
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PMID:Class II major histocompatibility complex-restricted T cells specific for a virion structural protein that do not recognize exogenous influenza virus. Evidence that presentation of labile T cell determinants is favored by endogenous antigen synthesis. 278 81

The three-dimensional structure of quinoprotein methylamine dehydrogenase from Thiobacillus versutus has been determined at 2.25 A resolution by a combination of multiple isomorphous replacement, phase extension by solvent flattening and partial structure phasing using molecular dynamics refinement. In the resulting map, the polypeptide chain for both subunits could be followed and an X-ray sequence was established. The tetrameric enzyme, made up of two heavy (H) and two light (L) subunits, is a flat parallellepiped with overall dimensions of approximately 76 x 61 x 45 A. The H subunit, comprising 370 residues, is made up of two distinct segments: the first 31 residues form an extension which embraces one of the L subunits; the remaining residues are found in a disc-shaped domain. This domain is formed by a circular arrangement of seven topologically identical four-stranded antiparallel beta-sheets, with approximately 7-fold symmetry. In spite of distinct differences, this arrangement is reminiscent of the structure found in influenza virus neuraminidase. The L subunit consists of 121 residues, out of which 53 form a beta-sheet scaffold of a central three-stranded antiparallel sheet flanked by two shorter two-stranded antiparallel sheets. The remaining residues are found in segments of irregular structure. This subunit is stabilized by six disulphide bridges, plus two covalent bridges involving the quinone co-factor and residues 57 and 107 of this subunit. The active site is located in a channel at the interface region between the H and L subunits, and the electron density in this part of the molecule suggests that the co-factor of this enzyme is not pyrrolo quinoline quinone (PQQ) itself, but might be instead a precursor of PQQ.
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PMID:Structure of quinoprotein methylamine dehydrogenase at 2.25 A resolution. 279 83

Shope fibroma virus (SFV), a tumorigenic poxvirus, has a 160-kb linear double-stranded DNA genome and possesses terminal inverted repeats (TIRs) of 12.4 kb. The DNA sequence of the terminal 5.5 kb of the viral genome is presented and together with previously published sequences completes the entire sequence of the SFV TIR. The terminal 400-bp region contains no major open reading frames (ORFs) but does possess five related imperfect palindromes. The remaining 5.1 kb of the sequence contains seven tightly clustered and tandemly oriented ORFs, four larger than 100 amino acids in length (T1, T2, T4, and T5) and three smaller ORFs (T3A, T3B, and T3C). All are transcribed toward the viral hairpin and almost all possess the consensus sequence TTTTTNT near their 3' ends which has been implicated for the transcription termination of vaccinia virus early genes. Searches of the published DNA database revealed no sequences with significant homology with this region of the SFV genome but when the protein database was searched with the translation products of ORFs T1-T5 it was found that the N-terminus of the putative T4 polypeptide is closely related to the signal sequence of the hemagglutinin precursor from influenza A virus, suggesting that the T4 polypeptide may be secreted from SFV-infected cells. Examination of other SFV ORFs shows that T1 and T2 also possess signal-like hydrophobic amino acid stretches close to their N-termini. The protein database search also revealed that the putative T2 protein has significant homology to the insulin family of polypeptides. In terms of sequence repetitions, seven tandemly repeated copies of the hexanucleotide ATTGTT and three flanking regions of dyad symmetry were detected, all in ORF T3C. A search for palindromic sequences also revealed two clusters, one in ORF T3A/B and a second in ORF T2. ORF T2 harbors five short sequence domains, each of which consists of a 6-bp short palindrome and a 10- to 18-bp larger palindrome. The significance of these palindromic domains in this ORF is unclear but the coincidence of the end of one larger palindrome with the end of the translated protein sequence that has homology with the B chain of insulin suggests that the palindromes may divide the T2 protein into several functional units. The salient organizational features of the complete SFV TIR are also discussed in light of what is known about other poxviral TIRs.
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PMID:Tumorigenic poxviruses: genomic organization and DNA sequence of the telomeric region of the Shope fibroma virus genome. 282 Jan 28

The M2 protein of influenza A virus is a small integral membrane protein of 97 residues that is expressed on the surface of virus-infected cells. M2 has an unusual structure as it lacks a cleavable signal sequence yet contains an ectoplasmic amino-terminal domain of 23 residues, a 19 residue hydrophobic transmembrane spanning segment, and a cytoplasmic carboxyl-terminal domain of 55 residues. Oligonucleotide-mediated deletion mutagenesis was used to construct a series of M2 mutants lacking portions of the hydrophobic segment. Membrane integration of the M2 protein was examined by in vitro translation of synthetic mRNA transcripts prepared using bacteriophage T7 RNA polymerase. After membrane integration, M2 was resistant to alkaline extraction and was converted to an Mr approximately equal to 7,000 membrane-protected fragment after digestion with trypsin. In vitro integration of M2 requires the cotranslational presence of the signal recognition particle. Deletion of as few as two residues from the hydrophobic segment of M2 markedly decreases the efficiency of membrane integration, whereas deletion of six residues completely eliminates integration. M2 proteins containing deletions that eliminate stable membrane anchoring are apparently not recognized by signal recognition particles, as these polypeptides remain sensitive to protease digestion, indicating that in addition they do not have a functional signal sequence. These data thus indicate that the signal sequence that initiates membrane integration of M2 resides within the transmembrane spanning segment of the polypeptide.
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PMID:Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus. 283 32

A collection of 39 influenza A virus strains of the subtype H3N2 isolated in G.D.R. and of six reference strains were analysed with regard to the antigenic structure of their surface proteins haemagglutinin (HA) and neuraminidase (NA) as well as regarding their polypeptide variations. For the field strains during the drift period from spring 1969 to spring 1980 seven main variations resulted from eight polyclonal sera with the haemagglutination inhibition test, and five main variations from six polyclonal sera with the neuraminidase inhibition test. Using the polyacrylamide gel electrophoresis polypeptide variations in HA, nonstructural proteins NS1, NS2 and nucleoprotein (NP) were detected. It could be shown that, even during one epidemic, strains circulated with different polypeptide composition. With the help of peptide mapping further variations of NP and NS1 were registered. The mechanisms leading to the emergence of new epidemic strains are discussed.
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PMID:Variation of influenza A (H3N2) viruses isolated in the G.D.R. during 1969-1980 epidemics. 287 20


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