Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulatory gene (degT) from Bacillus stearothermophilus NCA1503 which enhanced production of extracellular alkaline protease (Apr) was cloned in Bacillus subtilis with pTB53 as a vector. When B. subtilis MT-2 (Npr- [deficiency of neutral protease] Apr+) was transformed with the recombinant plasmid, pDT145, the plasmid carrier produced about three times more alkaline protease than did the wild-type strain. In contrast, when B. subtilis DB104 (Npr- Apr-) was used as a host, the transformant with pDT145 could not exhibit any protease activity. After construction of the deletion plasmids, DNA sequencing was done. A large open reading frame was found, and nucleotide sequence analysis showed that the degT gene was composed of 1,116 bases (372 amino acid residues, molecular weight of 41,244). A Shine-Dalgarno sequence was found nine bases upstream from the open reading frame. A B. subtilis strain carrying degT showed the following pleiotropic phenomena: (i) enhancement of production of extracellular enzymes such as alkaline protease and levansucrase, (ii) repression of autolysin activity, (iii) decrease of transformation efficiency for B. subtilis (competent cell procedure), (iv) altered control of sporulation, (v) loss of flagella, and (vi) abnormal cell division. When B. stearothermophilus SIC1 was transformed with the recombinant plasmid carrying degT, the transformants exhibited abnormal cell division. These phenomena are similar to those of the phenotypes of degSU(Hy) (hyperproduction), degQ(Hy), and degR mutants of B. subtilis. However, the amino acid sequence of the degT product (DegT) is different from those of the reported gene products. Furthermore, DegT includes a hydrophobic core region in the N-terminal portion (amino acid numbers 50 to 160), a consensus sequence for a DNA binding region (amino acid numbers 160 to 179), and a region homologous to transcription activator proteins (amino acid numbers 351 to 366). We discuss the possibility that the membrane protein DegT functions as a sensor protein and transfers the signal of environmental stimuli to the regulatory region of target genes to activate or repress transcription of the genes.
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PMID:Nucleotide sequence and cloning in Bacillus subtilis of the Bacillus stearothermophilus pleiotropic regulatory gene degT. 210 7

We have identified and characterized C3b binding proteins of two primates, orangutan (Pongo pygmaeus) and gorilla (Gorilla gorilla). Detergent solubilized 125I surface-labeled E and PBMC were subjected to affinity chromatography with homologous or human iC3/C3b. These ligands bound a 225,000 single chain protein from orangutan E and PBMC and a 220,000 protein from gorilla E. Proteins of the same Mr were immunoprecipitated by a rabbit polyclonal and two murine mAb to the human CR1 (CD35). The C3b binding protein of gorilla E aligned with that of the common human CR1 polymorphic size variant. Human or orangutan iC3 was also a ligand for a surface-labeled protein doublet of 59,000 and 65,000 from orangutan E. The doublet pattern and mol wts are similar to membrane cofactor protein (or CD46). Further, this doublet was immunoprecipitated by a mAb to human MCP. The MCP-like protein doublet was not isolated from gorilla or human E. Decay accelerating factor (DAF) of orangutan E was also identified and was structurally and antigenically distinct from the MCP-like protein. Orangutan or gorilla E preparations were a cofactor for the cleavage of human iC3 by human factor I and produced the same cleavage fragments as human CR1. Cofactor activity of orangutan E was partially inhibited by preclearance of CR1 and more completely inhibited by preclearance of MCP. Cofactor activity of gorilla E was inhibited by coincubation with a monoclonal antibody to human CR1. These data indicate that the orangutan and gorilla high m.w. proteins are equivalent to human CR1. The orangutan E membrane protein doublet with m.w. of 59,000 and 65,000 possesses biochemical, antigenic, and functional properties of human membrane cofactor protein.
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PMID:Characterization of CR1- and membrane cofactor protein-like proteins of two primates. 214 Mar 91

The complement receptors on macrophage are responsible for their binding and ingestion of opsonized targets. The two established receptors are CR1, which recognizes C3b, and CR3, which recognizes iC3b, the natural product of C3b from cleavage by the complement control protein factor I and its cofactors. CR1 belongs to a group of proteins that contain a structural element characterized by its size of 60-65 amino acids, and four conservatively positioned cysteines, which engage in a self-contained 1-3, 2-4 disulphide arrangement. This structural unit is called SCR (short consensus repeat) and is found in the complement proteins C1r, C1s, C2, factor B, factor H, C4BP, DAF, MCP and CR2, each of which interacts with some cleavage products of C3 and/or C4. CR1 has 30 SCR units accounting for its entire extracellular structure. It has a transmembrane segment and a small cytoplasmic domain. CR3 is a heterodimer containing an alpha and beta subunit held together by non-covalent forces. The beta subunit is also found in the two leukocyte antigens, LFA-1 and p150,95, which have alpha subunits distinct from that of CR3. The beta subunit contains 56 cysteine residues, 42 of which lie in a span of 256 residues immediately adjacent to the transmembrane segment. It shares extensive sequence homology with subunits of membrane protein complexes that bind fibronectin and vitronectin, implicating that they all belong to an extended set of surface adhesion molecules not restricted to the immune system. p150,95 is also expressed on macrophages and it has iC3b binding activity. It also shares some functional properties with CR3 as an adhesion surface molecule.
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PMID:C3 receptors on macrophages. 297 18

Membrane cofactor protein (MCP; formerly termed glycoprotein 45-70 to indicate its Mr) of complement is a widely distributed iC3/C3b binding protein with co-factor activity. On human mononuclear cells and cell lines and platelets, MCP is a doublet. The two forms differ in Mr by approximately 5 k and the upper species is predominant in most individuals. To further characterize these two forms, limited proteolytic digestions were performed. Of the four peptides produced, three have identical Mr indicating that the molecules are similar proteins. Both forms also have acidic isoelectric points and shift to a less acidic isoelectric point after treatment with neuraminidase. Glycosidase digestions indicate that both species contain N- and O-linked oligosaccharides but that the quantity of sialic acid is greater on the larger one. Pulse-chase experiments demonstrate approximately equal quantities of two precursor forms with Mr of 41 and 43 k. These two precursors possess N-linked high-mannose type of oligosaccharides and chase into the mature molecules which have complex sugars. The smaller precursor chases at a slower rate, possibly accounting for the reduced quantity of the smaller form of the mature form of MCP. These experiments indicate that the two forms of MCP are structurally similar and are derived from two distinct precursors. They also suggest that variations in the rate of processing of two intracellular precursors may account for the different quantities of the mature forms of this membrane protein.
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PMID:Biochemical characterization of membrane cofactor protein of the complement system. 305 3

In Escherichia coli, taxis to certain chemoeffectors is mediated through an intrinsic membrane protein called methyl-accepting chemotaxis protein I (MCP I), which is the product of the tsr gene. Mutants were selected that are defective in taxis toward all MCP I-mediated attractants (alpha-aminoisobutyrate, L-alanine, glycine, and L-serine) but are normal to MCP I-mediated repellents and to chemoeffectors mediated by other MCPs. The mutants could be divided into two classes based on their ability to respond to various concentrations of L-serine. Two MCP I-mediated L-serine systems appear to function in the wild type: one of high and one of lower affinity. The mutations responsible for the serine taxis defects map at about 99 min on the E. coli chromosome and are not complemented by episomes carrying mutations in the tsr gene; this suggests that they are defective in tsr function. Low concentrations of L-[14C]serine specifically bound to wild-type membranes with a Km of 5 microM; in contrast, there was greatly decreased binding to vesicles prepared from the new mutants or from the tsr mutant AW518. Binding of labeled serine to wild-type vesicles was inhibited by MCP I-mediated attractants, but not by MCP II-mediated attractants. The data suggest that MCP I may function as the L-serine chemoreceptor in E. coli.
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PMID:Genetic and biochemical properties of Escherichia coli mutants with defects in serine chemotaxis. 677 65

An in vitro system for the methylation of methyl-accepting chemotaxis proteins (MCP's), which have been shown to be membrane integral proteins, was constructed. The system, consisting of the membrane, the cytoplasm, and labeled S-adenosyl methionine, showed the following characteristics. 1. The methylation of MCP in the membrane required the cytoplasm. The rate of incorporation of the labeled methyl group into MCP was dependent on the amount of the cytoplasm. 2. Incorporation of the labeled methyl moiety into MCP reached a steady state, and the level of the steady state incorporation was dependent on the concentration of the cytoplasm when the concentration of the membrane protein was constant. 3. The methyl moiety which had been incorporated into MCP before the steady state could be exchanged. It was suggested that the amount of methyl group introduced into MCP was equal to that of taken from MCP. 4. The methylated MCP was demethylated faster in the presence of a methyl donor than in its absence. 5. The membranes obtained from cheX-, cheB-, and cheZ mutants were inactive in the present in vitro system even when they were mixed with the wild type cytoplasm.
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PMID:An in vitro study of the methylation of methyl-accepting chemotaxis protein of Escherichia coli. Construction of the system and effect of mutant proteins on the system. 701 48

Decay-accelerating factor (DAF) is a membrane protein that protects host cells from attack by its own complement. Although DAF expression on endothelial cells is thought to increase pathophysiologically, little is known about the natural mediators that modulate DAF expression on endothelial cells. In this study, we evaluated the effect of histamine on DAF expression on human umbilical vein cells (HUVEC). HUVEC were cultured with histamine, and DAF expression on HUVEC was determined by flow cytometry after immunostaining with a mAb to DAF. DAF expression on HUVEC was increased at 10 microM histamine, and the final level was increased time-dependently by 150% to 200% after a 24-h incubation with 100 microM histamine. The histamine-induced DAF expression was inhibited by actinomycin D and cycloheximide and accompanied by an increase in the DAF mRNA level, indicating that both transcription and translation are required. In addition, the histamine-induced DAF expression was inhibited by pyrilamine, an H1 blocker, but not by cimetidine, an H2 blocker, indicating that histamine induces the DAF expression through H1 receptors. We also demonstrated that the turnover of DAF is faster than that of MCP and CD59, and DAF is released into the culture supernatant. DAF is a glycosylphosphatidylinositol-linked protein that is released from HUVEC by a phosphatidylinositol-specific phospholipase C. Although HUVEC also contain the glycosylphosphatidylinositol-anchored complement inhibitor CD59, this was not released during a 24-h incubation, suggesting that the shedding of DAF from HUVEC is not caused by PI-PLC but by other enzymes, possibly proteinases. These results suggest that histamine, which is released from mast cells and basophils by complement-derived anaphylatoxins, increases the complement defense ability of endothelial cells by increasing their levels of DAF expression.
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PMID:Decay-accelerating factor on human umbilical vein endothelial cells. Its histamine-induced expression and spontaneous rapid shedding from the cell surface. 750 66

Multidrug resistance (MDR) to different cytotoxic compounds in the yeast Saccharomyces cerevisiae can arise from overexpression of the Pdr5 (Sts1, Ydr1, or Lem1) ATP-binding cassette (ABC) multidrug transporter. We have raised polyclonal antibodies recognizing the yeast Pdr5 ABC transporter to study its biogenesis and to analyze the molecular mechanisms underlying MDR development. Subcellular fractionation and indirect immunofluorescence experiments showed that Pdr5 is localized in the plasma membrane. In addition, pulse-chase radiolabeling of cells and immunoprecipitation indicated that Pdr5 is a short-lived membrane protein with a half-life of about 60 to 90 min. A dramatic metabolic stabilization of Pdr5 was observed in delta pep4 mutant cells defective in vacuolar proteinases, and indirect immunofluorescence showed that Pdr5 accumulates in vacuoles of stationary-phase delta pep4 mutant cells, demonstrating that Pdr5 turnover requires vacuolar proteolysis. However, Pdr5 turnover does not require a functional proteasome, since the half-life of Pdr5 was unaffected in either pre1-1 or pre1-1 pre2-1 mutants defective in the multicatalytic cytoplasmic proteasome that is essential for cytoplasmic protein degradation. Immunofluorescence analysis revealed that vacuolar delivery of Pdr5 is blocked in conditional end4 endocytosis mutants at the restrictive temperature, showing that endocytosis delivers Pdr5 from the plasma membrane to the vacuole.
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PMID:Endocytosis and vacuolar degradation of the plasma membrane-localized Pdr5 ATP-binding cassette multidrug transporter in Saccharomyces cerevisiae. 756 40

Group I Burkitt lymphoma (BL) lines retaining the original BL tumor cell phenotype are unable to present endogenously expressed antigens to HLA class I-restricted cytotoxic T cells (CTL) but can be recognized if the relevant HLA class I/peptide epitope complex is reconstituted at the cell surface by exogenous addition of synthetic target peptide. Endogenous antigen-processing function is restored in BL lines that have undergone Epstein-Barr virus (EBV)-induced drift in culture to the group III phenotype typically displayed by EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA-class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)-2, lmp-7 and delta, although the mb-1 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter-associated proteins (Tap), with down-regulation of Tap-1 and Tap-2 in 8/8 and 7/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap-deficient T2 processing-mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus-encoded latent membrane protein-1 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up-regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen-processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon-gamma treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen-processing function of BL cells, and suggest that the accessibility of other EBV-associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status.
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PMID:Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. 777 41

Signal peptides of gram-positive exoproteins generally carry a higher net positive charge at their amino termini (N regions) and have longer hydrophobic cores (h regions) and carboxy termini (C regions) than do signal peptides of Escherichia coli envelope proteins. To determine if these differences are functionally significant, the ability of Bacillus subtilis to secrete four different E. coli envelope proteins was tested. A pulse-chase analysis demonstrated that the periplasmic maltose-binding protein (MBP), ribose-binding protein (RBP), alkaline phosphatase (PhoA), and outer membrane protein OmpA were only inefficiently secreted. Inefficient secretion could be ascribed largely to properties of the homologous signal peptides, since replacing them with the B. amyloliquefaciens alkaline protease signal peptide resulted in significant increases in both the rate and extent of export. The relative efficiency with which the native precursors were secreted (OmpA >> RBP > MBP > PhoA) was most closely correlated with the overall hydrophobicity of their h regions. This correlation was strengthened by the observation that the B. amyloliquefaciens levansucrase signal peptide, whose h region has an overall hydrophobicity similar to that of E. coli signal peptides, was able to direct secretion of only modest levels of MBP and OmpA. These results imply that there are differences between the secretion machineries of B. subtilis and E. coli and demonstrate that the outer membrane protein OmpA can be translocated across the cytoplasmic membrane of B. subtilis.
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PMID:Escherichia coli signal peptides direct inefficient secretion of an outer membrane protein (OmpA) and periplasmic proteins (maltose-binding protein, ribose-binding protein, and alkaline phosphatase) in Bacillus subtilis. 818 2


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