UNIPROT:Q07644 - FACTA Search

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Query: UNIPROT:Q07644 (polypeptide)
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G proteins couple receptors for many hormones and neurotransmitters to effectors that regulate second messenger metabolism. G protein-coupled receptors comprise a superfamily with the common structural feature of a single polypeptide with seven membrane-spanning domains. G proteins themselves are heterotrimers with an alpha subunit that binds guanine nucleotides. In the basal state, G proteins tightly bind GDP; receptor activation allows exchange of bound GDP for GTP that activates the G protein and causes it to modulate effector activity. An intrinsic GTPase activity hydrolyzes bound GTP to GDP thereby deactivating the G protein. The effects (cholera, whooping cough) of bacterial toxins that target G proteins for covalent modification signal the potential importance of G protein dysfunction as a cause of human disease. Conceptually, G protein dysfunction could involve gain or loss of function. For Gs, examples of both types have already been defined. Mutations in G protein-coupled receptors have also been identified in several human diseases. Germline loss of function mutations in rhodopsin, cone opsins, the V2 vasopressin receptor, ACTH receptor, and calcium-sensing receptor are responsible for retinitis pigmentosa, color blindness, nephrogenic diabetes insipidus, familial ACTH resistance, and familial hypocalciuric hypercalcemia, respectively. Missense mutations that cause constitutive receptor activation have been identified in the TSH and LH receptors.
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PMID:Defects in G protein-coupled signal transduction in human disease. 881 89

Pertactin/P.69, a surface-associated polypeptide antigen of Bordetella pertussis, was expressed in a Salmonella typhimurium aroA aroD vaccine strain, BRD509, using different expression systems, and the immune response in mice against these constructs was compared. Initially, Pertactin/P.69 was expressed on the surface of BRD509 from a single copy of the gene encoding the antigen localized on the Salmonella chromosome. As previously shown, secretory and humoral antibody responses could not be detected following multiple immunization with this strain (BRD640). However, a strong anti-Pertactin/P.69 proliferative response was observed in murine splenocytes following a single oral dose with BRD640. The stimulated splenocytes secreted interferon-gamma but not interleukin-5, indicating that BRD640 induced a Th1 type T-helper response against Pertactin/P.69. We wished to construct a vaccine strain that might induce secretory and humoral responses against Pertactin/P.69 as well as a cell-mediated immune response. Consequently, Pertactin/P.69 was expressed at high levels in the cytoplasm of BRD509 under the control of the inducible nirB promoter from a ColE1-based replicon. Anti-Pertactin/P.69 immune responses were not observed following immunization of BALB/c mice with this strain (BRD975). Priming of the immune system against Pertactin/P.69 was, however, observed following oral immunization with BRD975 and boosting subcutaneously with purified Pertactin/P.69 antigen. The major anti-Pertactin/P.69 IgG subclass detected in boosted mice was IgG2a; thus, as BRD640, BRD975 appeared to induce a Th1 type T-helper response against Pertactin/P.69.
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PMID:Delivery of the Pertactin/P.69 polypeptide of Bordetella pertussis using an attenuated Salmonella typhimurium vaccine strain: expression levels and immune response. 900 50

The bvg or vir locus positively regulates the expression of many Bordetella virulence-associated determinants (encoded by vag genes), including cell envelope proteins, in response to environmental stimuli. On the other hand, several genes named vrg genes are negatively controlled by the bvg regulon (Knapp and Mekalanos, 1988). Flagellin is encoded by a vrg gene, which is expressed when the principal virulence factors are eliminated during antigenic modulation or in phase variants (Akerley et al., 1992). We have previously analyzed SDS-PAGE profiles of Sarkosyl-outer membrane protein (OMP)-enriched fractions from B. bronchiseptica Bvg- and modulated Bvg+ strains and reported a major band associated with the avirulent phenotype (Passerini de Rossi et al., 1995). In order to characterize this band we have purified flagellar filaments from Bvg- and modulated Bvg+ strains, and analyzed them by SDS-PAGE. These profiles revealed a single major band of 40 or 45 kDa depending on the strain. The N-terminal amino acid sequence of the putative flagellin expressed by BB7200a was identical over the first 21 residues analyzed to that of the flagellin from the modulated strain BB7865 reported by Akerley et al. (1992). Comparison of the SDS-PAGE profile of flagellar filaments with that of the OMP-enriched fraction of the corresponding strain showed that the flagellum-associated polypeptide had the same electrophoretic mobility as that of the characteristic band of the avirulent phenotype. Furthermore, this band was absent in the OMP-enriched fraction profile from a Bvg- strain subjected to a treatment that removes flagella. Our results indicate that the major protein observed in SDS-PAGE profiles of Sarkosyl-OMP-enriched fractions from B. bronchiseptica Bvg- and modulated Bvg+ strains corresponds to flagellin.
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PMID:Flagellin, a major protein present in SDS-PAGE profiles of Sarkosyl-OMP-enriched fractions from Bordetella bronchiseptica Bvg- or modulated Bvg+ strains. 922 83

In Rhizobium etli CFN42, both the symbiotic plasmid (pd) and plasmid b (pb) are required for effective bean nodulation. This is due to the presence on pb of a region (lps beta) involved in lipopolysaccharide (LPS) biosynthesis. We report here the genetic array and functional features of this plasmid-borne region. The sequence analysis of a 3,595-bp fragment revealed the presence of a transcriptional unit integrated by two open reading frames (lps beta 1 and lps beta 2) essential for LPS biosynthesis and symblosis. The lps beta 1 encodes a putative 193 amino acid polypeptide that shows strong homology with glucosyl-1P and galactosyl-1P transferases. The deduced amino acid sequence of the protein encoded by lps beta 2 was very similar to that of proteins involved in surface polysaccharide biosynthesis, such as Pseudomonas aeruginosa WpbM, Bordetella pertussis BpIL, and Yersinia enterocolitica TrsG. DNA sequences homologous to lps beta 1 and lps beta 2 of R. etli CFN42 were consistently found in functionally equivalent plasmids of R. etli, R. leguminosarum bv. viciae, and R. leguminosarum hv. trifolii strains, but not in R. meliloti, R. loti, R. tropici, R. fredii, Bradyrhizobium, Azorhizobium, and Agrobacterium tumefaciens. Even though Rhizobium and Agrobacterium do not share lps beta sequences, their presence is required for crown-gall tumor induction by R. etli transconjugants carrying the Ti plasmid.
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PMID:Characterization of two plasmid-borne lps beta loci of Rhizobium etli required for lipopolysaccharide synthesis and for optimal interaction with plants. 930 61

Adenylate cyclase toxin (CyaA) of Bordetella pertussis belongs to the RTX family of toxins. These toxins are characterized by a series of glycine- and aspartaterich nonapeptide repeats located at the C-terminal half of the toxin molecules. For activity, RTX toxins require Ca2+, which is bound through the repeat region. Here, we identified a stretch of 15 amino acids (block A) that is located C-terminally to the repeat and is essential for the toxic activity of CyaA. Block A is required for the insertion of CyaA into the plasma membranes of host cells. Mixing of a short polypeptide composed of block A and eight Ca2+ binding repeats with a mutant of CyaA lacking block A restores toxic activity fully. This in vitro interpolypeptide complementation is achieved only when block A is present together with the Ca2+ binding repeats on the same polypeptide. Neither a short polypeptide composed of block A only nor a polypeptide consisting of eight Ca2+ binding repeats, or a mixture of these two polypeptides, complement toxic activity. It is suggested that functional complementation occurs because of binding between the Ca2+ binding repeats of the short C-terminal polypeptide and the Ca2+ binding repeats of the CyaA mutant lacking block A.
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PMID:Characterization of the C-terminal domain essential for toxic activity of adenylate cyclase toxin. 998 38

The filamentous hemagglutinin (FHA) of Bordetella pertussis is a principal adhesin, which plays a key role in the colonization of the upper respiratory tract. FHA is also a protective antigen, which has been incorporated in the new generation of acellular vaccines against whooping cough. The protein is synthesized as a large 367-kDa precursor, which is then processed into a 220-kDa secreted polypeptide. To optimize the use of this protein for vaccine purposes it would be helpful to define the regions encompassing immunodominant epitopes. Twelve recombinant plasmids have been generated encoding fusion proteins between fragments of the matured-secreted 220-kDa form of FHA and the vector-encoded phage MS2 polymerase. Protein extracts of the resulting recombinant clones have been tested for reactivity with sera from 20 patients convalescent from whooping cough, and two human standard sera. The results indicate the presence of an immunodominant B cell epitope in the polypeptide coded by a 1-kb DNA fragment encompassing positions 5781-6800 of the published sequence. These results suggest that the identified fragment should be conserved in the formulation of vaccines against pertussis.
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PMID:Identification of immunodominant epitopes in the filamentous hemagglutinin of Bordetella pertussis. 1021 96

For most, if not all, organisms, iron (Fe) is an essential element. In response to the nutritional requirement for Fe, bacteria evolved complex systems to acquire the element from the environment. The genes encoding these systems are often coordinately regulated in response to the Fe concentration. Recent investigations revealed that Bordetella avium, a respiratory pathogen of birds, expressed a number of Fe-regulated genes (T. D. Connell, A. Dickenson, A. J. Martone, K. T. Militello, M. J. Filiatraut, M. L. Hayman, and J. Pitula, Infect. Immun. 66:3597-3605, 1998). By using manganese selection on an engineered strain of B. avium that carried an Fe-regulated alkaline phosphatase reporter gene, a mutant was obtained that was affected in expression of Fe-regulated genes. To determine if Fe-dependent regulation in B. avium was mediated by a fur-like gene, a fragment of the B. avium chromosome, corresponding to the fur locus of B. pertussis, was cloned by PCR. Sequencing revealed that the fragment from B. avium encoded a polypeptide with 92% identity to the Fur protein of B. pertussis. In vivo experiments showed that the cloned gene complemented H1780, a fur mutant of Escherichia coli. Southern hybridizations and PCRs demonstrated that the manganese mutant had a deletion of 2 to 3 kbp of nucleotide sequence in the region located immediately 5' of the fur open reading frame. A spontaneous PCR-derived mutant of the B. avium fur gene was isolated that encoded a Fur protein in which a histidine was substituted for an arginine at amino acid position 18 (R18H). Genetic analysis showed that the R18H mutant gene when cloned into a low-copy-number vector did not complement the fur mutation in H1780. However, the R18H mutant gene was able to complement the fur mutation when cloned into a high-copy-number vector. The cloned wild-type fur gene will be useful as a genetic tool to identify Fur-regulated genes in the B. avium chromosome.
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PMID:Genetic characterization of wild-type and mutant fur genes of Bordetella avium. 1033 37

Phenotypic analysis using heterologous host systems localized putative Bordetella pertussis ferric alcaligin transport genes and Fur-binding sequences to a 3.8-kb genetic region downstream from the alcR regulator gene. Nucleotide sequencing identified a TonB-dependent receptor family homolog gene, fauA, predicted to encode a polypeptide with high amino acid sequence similarity with known bacterial ferric siderophore receptors. In Escherichia coli, the fauA genes of both B. pertussis and Bordetella bronchiseptica directed the production of a 79-kDa polypeptide, approximating the predicted size of the mature FauA protein. B. bronchiseptica fauA insertion mutant BRM17 was unable to utilize ferric alcaligin, and in complementation analyses ferric alcaligin utilization was restored to this mutant by supplying the wild-type fauA gene in trans. Mutant BRM18, carrying a nonpolar in-frame fauA deletion mutation, was defective in ferric alcaligin utilization and (55)Fe-ferric alcaligin uptake and no longer produced a 79-kDa iron-regulated outer membrane protein. In complementation analyses, BRM18 merodiploids bearing the wild-type fauA gene in trans regained ferric alcaligin siderophore transport and utilization functions and produced the 79-kDa protein. Analysis of a plasmid-borne fauA-lacZ operon fusion confirmed that fauA is subject to iron regulation at the transcriptional level and that cis-acting transcriptional control elements mediating fauA iron repressibility reside within the 3.8-kb PstI fauA DNA region. Moreover, expression of the fauA-lacZ fusion gene under iron starvation conditions was shown to be alcR dependent. FauA is a 79-kDa iron-regulated outer membrane receptor protein required for transport and utilization of ferric alcaligin siderophore complexes by Bordetella species.
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PMID:Essential role of the iron-regulated outer membrane receptor FauA in alcaligin siderophore-mediated iron uptake in Bordetella species. 1049 7

Recently, the design of beta-sheet proteins and concomitant folding studies have attracted increasing attention. A unique natural all-beta domain occurs in a family of cytolytic bacterial toxins, the so-called RTX toxins. This domain consists of a variable number (about 6-45) of tandem repeats of a glycine-rich nine-residue motif with the consensus sequence GGXGXDX(L/I/F)X. The analysis of the three-dimensional structure of alkaline protease from Pseudomonas aeruginosa which possesses six of these repeats revealed that they fold into a novel 'parallel beta-roll' where calcium is bound within the turns connecting the beta-strands. A 75-mer peptide of the sequence NH(2)-WLS-[GGSGNDNLS](8)-COOH was chemically synthesised. Circular dichroism spectroscopy showed that this polypeptide folds in the presence of Ca(2+) and polyethylene glycol into a beta-structure which is presumably identical with the parallel beta-roll. This synthetic beta-roll behaves similarly to the isolated beta-roll domains from Escherichia coli haemolysin or Bordetella pertussis cyclolysin in terms of calcium binding and polymerisation behaviour.
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PMID:Folding of a synthetic parallel beta-roll protein. 1073 29

Macrolide antibiotics (Mac) consist of a 12- to 16-membered lactone ring combined with a sugar moiety, and they inhibit protein synthesis via binding to 23S ribosomal RNA in bacteria. The 14- and 16-membered Mac are used for treating infectious diseases caused by Gram-positive and other bacteria; e.g., Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Campylobacter, Treponema pallidum and Mycoplasma. Resistance to macrolide, lincosamide, and streptogramin-B (MLS) antibiotics in staphylococci is known to have the following mechanisms: 1) alteration of the target on ribosome due to dimethylation of a specific adenine residue in the 23S ribosomal RNA by the product of the erm gene, and consequently a decrease in binding of MLS antibiotics; 2) inactivation of streptogramin-B (STG-B) and lincosamide by the products of the sbh (encoding streptogramin B hydrolase) and linA' (encoding 3-lincomycin 4-clindamycin O-nucleotidyltransferase) genes, respectively; and 3) active efflux of Mac and STG-B antibiotics determined by the msrA and msrB genes in Staphylococcus epidermidis and Staphylococcus xylosus, respectively, both of which appear to act as an ATP-dependent efflux pump. I have shown that Staphylococcus aureus 8325(pEP2104) exhibits inducible resistance to PMS (partial macrolide and streptogramin B)-antibiotics [the 14-membered macrolides, erythromycin (EM), and oleandomycin (OL), and the 16-membered macrolide mycinamicin (MCM) and STG-B]. The sequence of the N-terminal amino acid residues of a 63 kDa protein (MsrSA) that appeared in the membrane of PMS-resistant strains was identical to that of an MsrA polypeptide related to enhanced efflux of [14C]EM. Ribosomes from PMS-resistant strains showed a similar affinity for EM to those from the PMS-sensitive host strain NCTC8325, and no inactivation of EM by 8325(pEP2104) was observed. In the present study, I showed the DNA sequence of the msrSA region on the constitutive PMS-resistant plasmid pMC38, PMS-inducible resistant plasmid pEP2104 and PMS-sensitive mutant plasmid pSP6, and the region that is essential for inducible expression in PMS resistance. In addition, I investigated the relationship between PMS resistance and intracellular accumulation of EM.
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PMID:[Study of macrolide, lincosamide, and streptogramin B antibiotics resistance in Staphylococcus aureus]. 1077 59

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