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Antigens of Mycobacterium tuberculosis Expressed during Preclinical Tuberculosis: Serological Immunodominance of Proteins with Repetitive Amino Acid Sequences

Singh, K. K.; Zhang, X.; Patibandla, A. S.; Chien, P.; Laal, S.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2001 EN
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45.96%
Four antigens of Mycobacterium tuberculosis that are expressed in vivo after aerosol infection but prior to the development of clinical tuberculosis (TB) in rabbits were identified by immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained 5 weeks postinfection. Three of the proteins identified, PirG (Rv3810), polymorphic GC-repetitive sequence (PE-PGRS; Rv3367), and proline-threonine repetitive protein (PTRP) (Rv0538), have multiple tandem repeats of unique amino acid sequences and have characteristics of surface or secreted proteins. The fourth protein, MtrA (Rv3246c), is a response regulator of a putative two-component signal transduction system, mtrA-mtrB, of M. tuberculosis. All four antigens were recognized by pooled sera from TB patients and not from healthy controls, confirming their in vivo expression during active infection in humans. Three of the antigens (PE-PGRS, PTRP, and MtrA) were also recognized by retrospective preclinical TB sera obtained, prior to the clinical manifestation of TB, from human immunodeficiency virus-TB patients, suggesting that they are potential candidates for devising diagnostic tests for active, preclinical TB.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions

Nishizawa, Manami; Nishizawa, Kazuhisa
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 01/10/2000 EN
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45.96%
The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the ‘between gene’ GC content heterogeneity...

Structural Proteins of Intracisternal A-Particles: Possible Repetitive Sequences

Marciani, Dante J.; Kuff, Edward L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1974 EN
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45.72%
Peptide maps of tryptic digests of the structural proteins from inner shells of intracisternal A-particles have shown common peptides for all the proteins. The terminal amino group of the three different structural proteins was identified as arginine. The major protein revealed approximately half the number of peptides expected from the amino acid composition. Since evidence for a cross-link bond has not been found, the main structural protein may be a single polypeptide chain containing a total or partial duplication of sequence.

Different evolutionary behavior of structurally related, repetitive sequences occurring in the same Balbiani ring gene in Chironomus tentans

Höög, Christer; Wieslander, Lars
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1984 EN
Relevância na Pesquisa
45.66%
The Balbiani ring 2 (BR 2) gene in Chironomus tentans is highly internally repeated. Two types of related repeat units—the α and β types—are tandemly arranged in separate blocks, which together are likely to form the major part of the gene. Every repeat unit has one constant region and one subrepeat region. Here we analyze the length and sequence of a number of repeat units of both types and compare the units within and between the blocks. The ≈100 α repeat units are essentially invariant regarding length and sequence. In contrast, when the ≈70 β repeat units are compared, six length variants are found, four of which have been sequenced. The length variations reside in the subrepeat regions and are due to different numbers of whole or half subrepeats. Furthermore, the subrepeat regions differ by several base-pair substitutions, many of which change the amino acid sequence. On the other hand, all β-type constant regions are of equal length and are virtually homogeneous in sequence. The observed length distributions in combination with analysis of the basepair substitutions in the α-and β-type constant and subrepeat regions suggest that the α and β blocks are of different age, that seemingly homologous repeated regions may play different functional roles at the protein level...

Repetitive Sequences in the Murein-Lipoprotein of the Cell Wall of Escherichia coli

Braun, V.; Bosch, V.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1972 EN
Relevância na Pesquisa
46.09%
The amino-acid sequence of the murein-lipoprotein of the Escherichia coli cell wall is presented. This protein is covalently bound to a lipid component as well as to the murein (peptidoglycan, mucopeptide). The sequence is also highly repetitive. At the N-terminal portion, there are three adjacent almost identical sequences, indicating repeated duplication of a gene coding originally for 15 amino acids. The C-terminal part of the polypeptide chain is more variable but still shows striking homology when certain sequence gaps are introduced. The lipid is bound to the N-terminal serine of the dipeptide (Ser-Ser) that extends from the repetitive sequence. At the C-terminal end where the murein is bound, a tripeptide extends from the repetitive portion. Here there are several basic amino acids and the only aromatic amino acid in the lipoprotein. The sequence is Lys-Tyr-Arg-Lys. The linkage to the murein is formed between the ε-amino group of the C-terminal lysine and the carboxyl group of the optical L-center of meso-diaminopimelic acid. The polypeptide chain is composed of 57 amino acids and lacks glycine, proline, cysteine, phenylalanine, histidine, and tryptophan. 63% of the amino acids are hydrophilic, but because of the covalently linked lipid this structural membrane protein has very hydrophobic properties.

Amino acid sequences around the sites of phosphorylation in the pig heart pyruvate dehydrogenase complex.

Sugden, P H; Kerbey, A L; Randle, P J; Waller, C A; Reid, K B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/1979 EN
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45.83%
1. When pig heart pyruvate dehydrogenase complex was phosphorylated to completion with [gamma-32P]ATP by its intrinsic kinase, three phosphorylation sites were observed. The amino acid sequences around these sites were: sequence 1, Tyr-Gly-Met-Gly-Thr-Ser(P)-Val-Glu-Arg; and sequence 2, Tyr-His-Gly-His-Ser(P)-Met-Ser-Asp-Pro-Gly-Val-Ser(P)-Tyr-Arg. 2. When phosphorylated to inactivation by repetitive additions of limiting quantities of [gamma-32P]ATP, phosphate was incorporated mainly (more than 90%) into Ser-5 of sequence 2. Phosphorylation of this site thus results in activation of pyruvate dehydrogenase. 3. If Ser-5 is phosphorylated with ATP and the enzyme then incubated with [gamma-32P]ATP, phosphorylation of the remaining sites occurred. Ser-12 of sequence 2 is phosphorylated about twice as rapidly as Ser-6 of sequence 1. 4. Incubation of pyruvate dehydrogenase with excess [gamma-32P]ATP with termination of phosphorylation at about 50% complete inactivation showed that Ser-5 of sequence 2 was phosphorylated most rapidly, but also that Ser-12 of sequence 2 was significantly (15% of total) phosphorylated. Ser-6 sequence 1 contained about 1% total P. 5. These results suggest that addition of limiting amounts of ATP produces primarily phosphorylation of Ser-5 of sequence 2 (inactivating site). This also occurs during incubation with excess ATP before complete inactivation occurs...

A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA

Shen, Li; Gao, Ge; Zhang, Ying; Zhang, He; Ye, Zhiqiang; Huang, Shichao; Huang, Jinyan; Kang, Jiuhong
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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45.91%
Dnmt3a and Dnmt3b are paralogous enzymes responsible for de novo DNA methylation but with distinguished biological functions. In mice, disruption of Dnmt3b but not Dnmt3a causes global DNA hypomethylation, especially in repetitive sequences, which comprise the large majority of methylated DNA in the genome. By measuring DNA methylation activity of Dnmt3a and Dnmt3b homologues from five species, we found that mammalian Dnmt3b possessed significantly higher methylation activity on chromatin DNA than Dnmt3a and non-mammalian Dnmt3b. Sequence comparison and mutagenesis experiments identified a single amino acid substitution (I662N) in mammalian Dnmt3b as being crucial for its high chromatin DNA methylation activity. Further mechanistic studies demonstrated this substitution markedly enhanced the binding of Dnmt3b to nucleosomes and hence increased the chromatin DNA methylation activity. Moreover, this substitution was crucial for Dnmt3b to efficiently methylate repetitive sequences, which increased dramatically in mammalian genomes. Consistent with our observation that Dnmt3b evolved more rapidly than Dnmt3a during the emergence of mammals, these results demonstrated that the I662N substitution in mammalian Dnmt3b conferred enhanced chromatin DNA methylation activity and contributed to functional adaptation in the epigenetic system.

Strategy for complete NMR assignment of disordered proteins with highly repetitive sequences based on resolution-enhanced 5D experiments

Motáčková, Veronika; Nováček, Jiří; Zawadzka-Kazimierczuk, Anna; Kazimierczuk, Krzysztof; Žídek, Lukáš; Šanderová, Hana; Krásný, Libor; Koźmiński, Wiktor; Sklenář, Vladimír
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.86%
A strategy for complete backbone and side-chain resonance assignment of disordered proteins with highly repetitive sequence is presented. The protocol is based on three resolution-enhanced NMR experiments: 5D HN(CA)CONH provides sequential connectivity, 5D HabCabCONH is utilized to identify amino acid types, and 5D HC(CC-TOCSY)CONH is used to assign the side-chain resonances. The improved resolution was achieved by a combination of high dimensionality and long evolution times, allowed by non-uniform sampling in the indirect dimensions. Random distribution of the data points and Sparse Multidimensional Fourier Transform processing were used. Successful application of the assignment procedure to a particularly difficult protein, δ subunit of RNA polymerase from Bacillus subtilis, is shown to prove the efficiency of the strategy. The studied protein contains a disordered C-terminal region of 81 amino acids with a highly repetitive sequence. While the conventional assignment methods completely failed due to a very small differences in chemical shifts, the presented strategy provided a complete backbone and side-chain assignment.

Human Protein Cluster Analysis Using Amino Acid Frequencies

Vernone, Annamaria; Berchialla, Paola; Pescarmona, Gianpiero
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/04/2013 EN
Relevância na Pesquisa
45.88%
The paper focuses on the development of a software tool for protein clustering according to their amino acid content. All known human proteins were clustered according to the relative frequencies of their amino acids starting from the UniProtKB/Swiss-Prot reference database and making use of hierarchical cluster analysis. Results were compared to those based on sequence similarities. Results: Proteins display different clustering patterns according to type. Many extracellular proteins with highly specific and repetitive sequences (keratins, collagens etc.) cluster clearly confirming the accuracy of the clustering method. In our case clustering by sequence and amino acid content overlaps. Proteins with a more complex structure with multiple domains (catalytic, extracellular, transmembrane etc.), even if classified very similar according to sequence similarity and function (aquaporins, cadherins, steroid 5-alpha reductase etc.) showed different clustering according to amino acid content. Availability of essential amino acids according to local conditions (starvation, low or high oxygen, cell cycle phase etc.) may be a limiting factor in protein synthesis, whatever the mRNA level. This type of protein clustering may therefore prove a valuable tool in identifying so far unknown metabolic connections and constraints.

An Amino Acid Packing Code for α-helical Structure and Protein Design

Joo, Hyun; Chavan, Archana G.; Phan, Jamie; Day, Ryan; Tsai, Jerry
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.82%
This work demonstrates that all packing in α-helices can be simplified to repetitive patterns of a single motif: the knob-socket. Using the precision of Voronoi Polyhedra/Deluaney Tessellations to identify contacts, the knob-socket is a 4 residue tetrahedral motif: a knob residue on one α-helix packs into the 3 residue socket on another α-helix. The principle of the knob-socket model relates the packing between levels of protein structure: the intra-helical packing arrangements within secondary structure that permit inter-helix tertiary packing interactions. Within an α-helix, the 3 residue sockets arrange residues into a uniform packing lattice. Inter-helix packing results from a definable pattern of interdigitated knob-socket motifs between 2 α-helices. Furthermore, the knob-socket model classifies 3 types of sockets: 1) free: favoring only intra-helical packing, 2) filled: favoring inter-helical interactions and 3) non: disfavoring α-helical structure. The amino acid propensities in these 3 socket classes essentially represent an amino acid code for structure in α-helical packing. Using this code, a novel yet straightforward approach for the design of α-helical structure was used to validate the knob-socket model. Unique sequences for 3 peptides were created to produce a predicted amount of α-helical structure: mostly helical...

Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae

Morona, J.; Morona, R.; Miller, D.; Paton, J.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2003 EN
Relevância na Pesquisa
45.77%
In Streptococcus pneumoniae, CpsB, CpsC, and CpsD are essential for encapsulation, and mutants containing deletions of cpsB, cpsC, or cpsD exhibit rough colony morphologies. CpsD is an autophosphorylating protein-tyrosine kinase, CpsC is required for CpsD tyrosine phosphorylation, and CpsB is a phosphotyrosine-protein phosphatase. We have previously shown that autophosphorylation of CpsD at tyrosine attenuates its activity and consequently reduces the level of encapsulation and negatively regulates CPS production. In this study, we further investigated the role of the carboxy-terminal (YGX)4 repeat domain of CpsD in encapsulation. A CpsD truncation mutant in which the entire (YGX)4 repeat domain was removed was indistinguishable from a strain in which the entire cpsD gene had been deleted, indicating that the carboxy-terminal (YGX)4 tail is required for CpsD activity in capsular polysaccharide production. Double mutants having a single tyrosine residue at position 2, 3, or 4 in the (YGX)4 repeat domain and lacking CpsB exhibited a rough colony morphology, indicating that in the absence of an active protein-tyrosine phosphatase, phosphorylation of just one of the tyrosine residues in the (YGX)4 repeat was sufficient to inactivate CpsD. When various mutants in which CpsD had either one or combinations of two or three tyrosine residues in the (YGX)4 repeat domain were examined...

Identification of the gene FMR2, associated with FRAXE mental retardation

Gecz, J.; Gedeon, A.; Sutherland, G.; Mulley, J.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
Relevância na Pesquisa
45.85%
Five folate-sensitive fragile sites have been characterized at the molecular level (FRAXA, FRAXE, FRAXF, FRA16A and FRA11B). Three of them (FRAXA, FRAXE and FRA11B) are associated with clinical problems, and two of the genes (FMR1 in FRAXA and CBL2 in FRA11B) have been identified. All of these fragile sites are associated with (CCG)n/(CGG)n triplet expansions which are hypermethylated beyond a critical size. FRAXE is a rare folate sensitive fragile site only recently recognized. Its cytogenetic expression was found to involve the amplification of a (CCG)n repeat adjacent to a CpG island. Normal alleles vary from 6 to 25 copies. Expansions of greater than 200 copies were found in FRAXE expressing males and their FRAXE associated CpG island was fully methylated. An association of FRAXE expression with concurrent methylation of the CpG island and mild non-specific mental handicap in males has been reported by several groups. We now report the cloning and characterization of a gene (FMR2) adjacent to FRAXE. Elements of FMR2 were initially identified from sequences deleted from a developmentally delayed boy. We correlate loss of FMR2 expression with (CCG)n expansion at FRAXE, demonstrating that this is a gene associated with the CpG island adjacent to FRAXE and contributes for FRAXE-associated mild mental retardation.; Jozef Gecz...

The Aspergillus nidulans creC gene involved in carbon catabolite represssion encodes a WD40 repeat protein

Todd, R.; Lockington, R.; Kelly, J.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Publicado em //2000 EN
Relevância na Pesquisa
45.82%
Expression of many microbial genes required for the utilisation of less favoured carbon sources is carbon catabolite repressed in the presence of a preferred carbon source such as D-glucose. In Aspergillus nidulans, creC mutants show derepression in the presence of D-glucose of some, but not all, systems normally subject to carbon catabolite repression. These mutants also fail to grow on some carbon sources, and show minor morphological impairment and altered sensitivity to toxic compounds including molybdate and acriflavin. The pleiotropic nature of the phenotype suggests a role for the creC gene product in the carbon regulatory cascade. The creC gene was cloned and found to encode a protein which contains five WD40 motifs. The sequence changes in three mutant alleles were found to lead to production of truncated proteins which lack one or more of the WD40 repeats. The similarity of the phenotypes conferred by these alleles implies that these alleles represent loss of function alleles. Deletion analysis also showed that at least the most C-terminal WD40 motif is required for function. The CreC protein is highly conserved relative to the Schizosaccharomyces pombe protein Yde3 – whose function is unknown – and human and mouse DMR-N9...

RcoA has pleiotropic effects on aspergillus nidulans cellular development

Hicks, J.; Lockington, R.; Strauss, J.; Dieringer, D.; Kubicek, C.; Kelly, J.; Keller, N.
Fonte: Blackwell Science Ltd Publicador: Blackwell Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2001 EN
Relevância na Pesquisa
45.82%
Aspergillus nidulans rcoA encodes a member of the WD repeat family of proteins. The RcoA protein shares sequence similarity with other members of this protein family, including the Saccharomyces cerevisiae Tup1p and Neurospora crassa RCO1. Tup1p is involved in negative regulation of an array of functions including carbon catabolite repression. RCO1 functions in regulating pleiotropic developmental processes, but not carbon catabolite repression. In A. nidulans, deletion of rcoA (DrcoA), a recessive mutation, resulted in gross defects in vegetative growth, asexual spore production and sterigmatocystin (ST) biosynthesis. Expression of the asexual and ST pathway-specific regulatory genes, brlA and aflR, respectively, but not the signal transduction genes (i.e. flbA, fluG or fadA) regulating brlA and aflR expression was delayed (brlA) or eliminated (aflR) in a DrcoA strain. Overexpression of aflR in a DrcoA strain could not rescue normal expression of downstream targets of AflR. CreAdependent carbon catabolite repression of starch and ethanol utilization was only weakly affected in a DrcoA strain. The strong role of RcoA in development, vegetative growth and ST production, compared with a relatively weak role in carbon catabolite repression...

The human complement regulator factor H binds pneumococcal surface protein PspC via short consensus repeats 13 to 15

Duthy, T.; Ormsby, R.; Giannakis, E.; Ogunniyi, A.; Stroeher, U.; Paton, J.; Gordon, D.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
Relevância na Pesquisa
45.66%
The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system. One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack. The pneumococcal surface protein C (PspC [also known as CbpA] and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known. The purpose of the current study was to map specific SCRs on fH responsible for this binding. Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC mutant) showed that fH binding was PspC dependent. A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspCPro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction. We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic...

Conserved sequences flank variable tandem repeats in two S-antigen genes of Plasmodium falciparum

Cowman, A.F.; Saint, R.B.; Coppel, R.L.; Brown, G.V.; Anders, R.R.; Kemp, D.J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //1985 EN
Relevância na Pesquisa
55.87%
We describe the isolation of two chromosomal DNA fragments from Plasmodium falciparum. These fragments encode the antigenically distinct S antigens of two different P. falciparum isolates, namely FC27 from Papua New Guinea and NF7 from Ghana. The complete nucleotide sequences of both fragments are presented. The fragments are homologous over most of their lengths, including the entire regions flanking the protein coding sequences. Whereas the N- and C-terminal portions of sequences encoding the S antigens are homologous, major portions of the coding sequences are not. The nonhomologous regions are comprised of tandemly repeated sequences, of 33 by in FC27 and predominantly of 24 by in NF7. The 33 by tandem repeats encoded by the FC27 S-antigen gene could not be detected in the NF7 genome. Conversely, the 24 by tandem repeats encoded by the NF7 S-antigen gene could not be detected in the FC27 genome. The pattern of sequence variation within the repeats of both genes suggests a mechanism for the generation of S-antigen diversity.; Alan F. Cowman, Robert B. Saint, Ross L. Coppel, Graham V. Brown, Robin R. Andere, David J. Kemp

Removal of the four c-terminal glycine-rich repeats enhances the thermostability and substrate binding affinity of barley b-amylase

Ma, Y.; Eglinton, J.; Evans, D.; Logue, S.; Langridge, P.
Fonte: Amer Chemical Soc Publicador: Amer Chemical Soc
Tipo: Artigo de Revista Científica
Publicado em //2000 EN
Relevância na Pesquisa
45.77%
Barley beta-amylase undergoes proteolytic cleavage in the C-terminal region after germination. The implication of the cleavage in the enzyme's characteristics is unclear. With purified native beta-amylases from both mature barley grain and germinated barley, we found that the beta-amylase from germinated barley had significantly higher thermostability and substrate binding affinity for starch than that from mature barley grain. To better understand the effect of the proteolytic cleavage on the enzyme's thermostability and substrate binding affinity for starch, recombinant barley beta-amylases with specific deletions at the C-terminal tail were generated. The complete deletion of the four C-terminal glycine-rich repeats significantly increased the enzyme's thermostability, but an incomplete deletion with one repeat remaining did not change the thermostability. Although different C-terminal deletions affect the thermostability differently, they all increased the enzyme's affinity for starch. The possible reasons for the increased thermostability and substrate binding affinity, due to the removal of the four C-terminal glycine-rich repeats, are discussed in terms of the three-dimensional structure of beta-amylase.; Yue F. Ma, Jason K. Eglinton...

Comparative toxicity of polyglutamine, polyalanine and polyleucine tracts in Drosophila models of expanded repeat disease

van Eyk, C.; McLeod, C.; O'Keefe, L.; Richards, R.
Fonte: Oxford Univ Press Publicador: Oxford Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
65.89%
Homopolymeric amino acid repeat sequences in proteins are of particular interest due to the discovery that expanded copy numbers of these repeats are the molecular basis for a growing list of human genetic diseases. Repeat copy numbers above a typical normal range of polyglutamine repeats have been found to be the principal pathogenic agents in a number of these diseases, including Huntington's disease. There is emerging evidence that expansions of amino acids encoded by other reading frames of CAG/CUG repeats, including polyalanine and polyleucine, could contribute to toxicity in the 'polyglutamine' diseases. We have therefore used the Drosophila model system to investigate effects of ectopic expression of polyglutamine, polyleucine and polyalanine repeats in vivo to assess their relative toxicities and the common and distinct characteristics of the pathogenesis that they cause. We find that these homopolymeric sequences all exhibit toxicity and are able to form aggregates in Drosophila, although there are marked differences in the degree of toxicity dependent upon the tissue in which they are expressed.; Clare L. van Eyk, Catherine J. McLeod, Louise V. O'Keefe and Robert I. Richards

DNA binding by the coliphage 186 repressor protein C1

Dodd, I.; Egan, J.
Fonte: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Publicador: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
Relevância na Pesquisa
45.8%
The cI gene of coliphage 186 maintains lysogeny and confers immunity to 186 infection by repressing the major early promoter, p(R), and the promoter for the late transcription activator gene, p(B). Gel mobility shirt and DNase I footprinting show that CI protein binds to the DNA at p(R) and p(B) and also to sites approximately 300 base pairs upstream and downstream of p(R), called FL and FR. Mutations which cause virulence reduce CI binding to p(R). The biochemical and genetic data identify three CI operators at p(R), two at p(B), and single operators at FL and FR. The operators at the p(B), FL, FR, and central p(R) sites are inverted repeat sequences, separated by 5 base pairs (Type A) or, in the case of p(R), by 4 base pairs (Type A'). A different inverted repeat operator sequence (Type B) is proposed for the binding sites on each side of the central site at p(R). Thus, CI appears to recognize two distinct DNA sequences. CI binds cooperatively to adjacent operators, and binding at p(R) is strongly dependent on these cooperative interactions. A high order CI multimer appears to be the active DNA binding species, even at single operators.

Characterization and chromosomal localization of the human A2a adenosine receptor gene - ADORA2A

Le, F.; Townsend-Nicholson, A.; Baker, E.; Sutherland, G.; Schofield, P.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
Relevância na Pesquisa
45.77%
The gene for the stimulatory G protein-coupled human A2a adenosine receptor was isolated and sequence analysis revealed two exons that are interrupted by an intron of approximately 6.4 kb. An intron is located in the same region in the human A1 and A2b adenosine receptor genes. Comparison of the A2a genomic and cDNA sequences reveals two nucleotide differences in the coding region and the presence of an aberrant sequence in the 5'208 base pairs of the A2a cDNA including a polymorphism in the third base of codon Tyr-361 and Gly codon which was always detected at residue 392, indicated that the Arg codon present in the cDNA may be an artifact. Fluorescent in situ hybridization and PCR analysis of human-hamster hybrid cell panels shows that the A2a receptor gene is localized to chromosome 22q11.2. This is in contrast with previous reports (subsequently retracted) which mapped the A2a gene to chromosome 11q11-13.; Le, Fei ; Townsend-Nicholson, Andrea ; Baker, Elizabeth ; Sutherland, Grant R. ; Schofield, Peter R.