| 2456210 |
Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains |
10.1002/j.1460-2075.1988.tb02867.x. |
EMBO J |
Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains
Abstract
- CD20 is an antigen expressed on normal and malignant human B cells that is thought to function as a receptor during B cell activation. Here we report the isolation of a CD20-specific cDNA clone from a lambda gt11 library using a polyclonal antiserum raised against purified CD20 antigen. Additional cDNA clones were then isolated from a lambda gt10 library. Alignment of the sequences of overlapping lambda clones reveal a single consensus sequence except for a divergence that preceded the first methionine within the open reading frame. Normal B cells and B cell lines contain a prominent 2.6 kb mRNA and a lower level of a 3.3 kb mRNA. An oligonucleotide derived from one of the divergent sequences hybridized to the 3.3 kb mRNA only, indicating that the two mRNA species are derived from an alternative splicing mechanism. The predicted amino acid sequence of CD20 reveals three major hydrophobic regions of approximately 53, 25 and 20 amino acids. CD20 lacks an NH2-terminal signal peptide and contains a highly charged COOH-terminal domain. Although CD20 is immunoprecipitated as a doublet of 33 and 35 kd proteins from B cells, in vitro translation of CD20 cDNA produced a single 33 kd protein that was specifically immunoprecipitated with monoclonal CD20 antibodies. CD20 was strongly phosphorylated on resting B cells after CDw40 stimulation, suggesting that CD20 may be functionally regulated by a protein kinase(s).
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| 2461859 |
Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity. |
10.1111/j.1432-1033.1988.tb14404.x |
Eur. J. Biochem. |
Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity.
Abstract
- We have isolated three different monoclonal antibodies specific for mammalian type-I DNA topoisomerase. The antibodies react with three closely adjacent epitopes located in a central section of the enzyme (between amino acid residues 344 and 483). Two of the antibodies inhibit an early step of the nicking/closing pathway. We provide evidence showing that the antibodies do not block the association of the enzyme with DNA. The antibodies are useful for immunocytochemical investigation and for further exploration of the biochemical function of mammalian type-I DNA topoisomerase.
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| 2466899 |
Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1) |
None |
J Immunol |
Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1)
Abstract
- The CD20 (B1) molecule is a differentiation Ag found only on the surface of B lymphocytes. This structurally unique phosphoprotein plays a role in the regulation of human B cell proliferation and differentiation. In this report genomic DNA clones containing the human CD20 gene were isolated and the structure of the CD20 gene determined. Southern blot analysis revealed that CD20 mRNA was transcribed from a single-copy gene. The CD20 gene was 16 kb long and was composed of eight exons. The first exon marked the major transcription initiation site as determined by primer extension and S1 nuclease analysis. The translation initiation codon was located within the third exon. Exon VIII encoded the COOH terminus of the CD20 protein and the long 3' untranslated region. Three forms of CD20 mRNA were identified that all encode an identical protein product. The dominant form of 2.8 kb results from usage of exons I through VIII, whereas a second form that is 263 bp shorter had exon I spliced into an internal 3' splice site within exon III thereby skipping exon II. A minor 3.4-kb mRNA species most likely results from an uncharacterized upstream exon(s) splicing into an internal 3' slice site located in exon I. Nucleotide sequences of cDNA clones representative of each of these RNA forms are presented. The 5' splice site following exon V was found to be divergent from the consensus splice sequence. A relationship between the individual peptides encoded by the six exons and structurally distinct regions of the CD20 protein is likely.
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| 2468617 |
Modulation by drugs of eosinophil recruitment induced by immune challenge in the rat. Possible roles of interleukin 5 and platelet-activating factor |
10.1159/000234790. |
Int Arch Allergy Appl Immunol |
Modulation by drugs of eosinophil recruitment induced by immune challenge in the rat. Possible roles of interleukin 5 and platelet-activating factor
Abstract
- The factors responsible for eosinophil recruitment are poorly defined, although both platelet-activating factor (PAF) and cytokines appear to be involved in regulating this process. We compared eosinophil mobilization induced by PAF or antigen injection in the peritoneal cavity of hypereosinophilic rats and the effects of the PAF antagonist BN 52021, the somatostatin analog BIM 23014, and cyclosporin A on this process. PAF induced a significant increase of both peritoneal and circulating eosinophil count. Cyclosporin A almost totally abrogated these variations, whereas BN 52021 reduced the peritoneal increase. Similarly to PAF, peritoneal antigen challenge in actively sensitized animals increased peritoneal and circulating eosinophil counts. Cyclosporin A abolished both hypereosinophilia and peritoneal eosinophil infiltration. BIM 23014 reduced the circulating eosinophils and cell infiltration. In contrast, BN 52021 primarily decreased peritoneal eosinophil recruitment, while having little effect on circulating cells. The different mechanisms of action of these drugs and the involvement of interleukin 5 in eosinophil recruitment are discussed.
|
| 2470418 |
Ionic pores formed by cyclic peptides |
10.1016/0300-9084(89)90134-x. |
Biochimie |
Ionic pores formed by cyclic peptides
Abstract
- It is shown that 2 cyclic tetrapeptides, namely tentoxin and HC toxin, are able to induce the formation of transmembrane ionic channels, although a carrier mechanism could be expected on the basis of their chemical structure (presence of proline or N-methylated residues). Since other cyclic peptides but of larger size, i.e., tyrocidines, gramicidin S (decapeptides) and an octapeptide with a sequence similar to that of HC toxin, are also able to form pores, it appears that this property can be extended to a large number of cyclic peptides. A pore structure based on aggregates is proposed.
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| 2479024 |
Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis. |
10.1073/pnas.86.21.8492 |
Proc. Natl. Acad. Sci. U.S.A. |
Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis.
Abstract
- The possibility that viruses play a role in the etiology of various autoimmune diseases has been proposed. One approach to the search for these agents involves identifying potential crossreactive epitopes in viruses that infect cells of the immune system or of the target tissues. Antibodies to DNA topoisomerase I are the marker autoantibodies for diffuse systemic sclerosis. The major epitope of the antigen was therefore sought through cloning and sequencing of the cDNA for human topoisomerase I and eventually by the synthesis of the smallest possible peptide recognized by sera from patients with the diffuse form of systemic sclerosis. The antigenic 11-amino acid sequence contains 6 sequential amino acids that are identical to a sequence present in the group-specific antigen (p30gag) of some mammalian retroviruses. This sequence is separated by only 1 amino acid from the retroviral epitope sequence that crossreacts with autoantibodies against the marker antigen for mixed connective-tissue disease and systemic lupus erythematosus, the 70-kDa polypeptide of U1 ribonucleoprotein particles. These findings suggest that a retroviral agent may be involved in the pathogenesis of systemic sclerosis and other connective tissue diseases and that antibodies to intracellular antigens are not involved in the pathogenesis of autoimmune disease but may be useful as footprints for tracking the potential etiological agent of autoimmune disease.
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| 2479553 |
A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance |
10.1002/j.1460-2075.1989.tb08387.x. |
EMBO J |
A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance
Abstract
- We have determined the primary structure of a mutant insulin receptor of a leprechaun patient born from a consanguineous marriage. A characteristic feature of leprechaunism is an extreme resistance to insulin. In this patient the insulin resistance seems to result from an observed lack of insulin binding to intact cells. Solubilization of cells in non-ionic detergents leads to the appearance of insulin receptors which can bind insulin. However, the insulin-stimulated autophosphorylation of the receptor's beta subunit is markedly reduced. Cloning and sequencing of cDNA derived from insulin receptor mRNA of this patient revealed a leucine-to-proline mutation at position 233 in the alpha subunit. By means of DNA amplification we found that the patient is homozygous for this mutation and that the parents and two grandparents from the consanguineous line are heterozygous. The heterozygous individuals all show decreased insulin binding to cultured fibroblasts. In addition, they are mildly insulin resistant in vivo. These observations show a linkage between the leucine-to-proline mutation and the observed insulin resistance in this family. We therefore conclude that the mutation in the homozygous form is responsible for the extreme insulin resistance in the leprechaun patient. The mutation for the first time characterizes a region in the insulin receptor which seems to be involved in transmitting the insulin binding signal to the tyrosine kinase domain.
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| 2482262 |
Conformations, cation binding, and transmembrane ion transfer properties of a cyclooctapeptide built by an alternation of D and L residues |
10.1111/j.1399-3011.1989.tb00707.x. |
Int J Pept Protein Res |
Conformations, cation binding, and transmembrane ion transfer properties of a cyclooctapeptide built by an alternation of D and L residues
Abstract
- The conformations of a cyclic octapeptide built with an alternation of D and L residues are investigated on the basis of 1H n.m.r. and CD data. The cyclooctapeptide can form structures which are specific to the alternating D-L sequence. This peptide can form two types of complexes with cations (peptide 2-cation and peptide-cation complexes) and the binding with monovalent cation is weak. This peptide is able to induce transmembrane ion transfer through both a carrier mechanism and pore formation.
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| 2484929 |
Molecular conformation and ion transport of cyclic and linear ionophores |
10.1016/s0263-7855(89)80004-9. |
J Mol Graph |
Molecular conformation and ion transport of cyclic and linear ionophores
Abstract
- X-ray crystal structure determinations and energy-minimization techniques provide conformational data on the complexed and uncomplexed forms of ion transport antibiotics of the shuttle and channel types. In the solid state, hexadecaisoleucinomycin (HEXIL), an analogue of valinomycin, is observed as an asymmetric macrocycle stabilized by eight intramolecular (4----1) hydrogen bonds. The structure obtained from energy-minimization procedures exhibits a greater variation in phi and psi angles of chemically equivalent residues than does the crystallographically observed structure. The structure has eight carbonyl groups directed toward its interior and is capable of providing flexible coordination to a positively charged ion or molecule. These structural findings are consistent with the observed capacity of HEXIL to complex cesium ions, tetramethyl ammonium ions and acetylcholine. Gramicidin A is a pentadecapeptide that functions as a transmembrane channel for transporting monovalent cations. Uncomplexed gramicidin A crystallizes as a left-handed, antiparallel, double-stranded, helical dimer with 5.6 amino acid residues per turn. The helix has an overall length of 31 A and an average inner channel diameter of 4.8 A. The channel of this crystalline form does not contain ions or solvent molecules. Transporting ions through this channel could be achieved only by some expansion of the channel opening that would involve breaking and reforming hydrogen bonds that stabilize the double-stranded helix.
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| 2492662 |
Structural characterization of toxic cyclic peptides from blue-green algae by tandem mass spectrometry |
10.1073/pnas.86.3.770. |
Proc Natl Acad Sci U S A |
Structural characterization of toxic cyclic peptides from blue-green algae by tandem mass spectrometry
Abstract
- Combined use of chemical degradation, derivatization, and tandem mass spectrometry for rapid structural characterization of toxic cyclic peptides from blue-green algae at the nanomole level is described. Previously, all blue-green algal toxins were thought to belong to a family of seven-residue cyclic peptides, having the general structure cyclo-D-Ala-L-Xaa-erythro-beta-methyl-D-isoaspartic acid-L-Yaa-Adda-D-isoglutamic acid-N-methyldehydroalanine, where Xaa and Yaa represent variable amino acids of the L configuration and Adda is 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid. Structural characterization of two additional toxins indicates that further variability can exist within this family of naturally occurring toxic cyclic peptides. Isoaspartic acid and dehydroalanine can substitute for beta-methylisoaspartic acid and N-methyldehydroalanine, respectively.
|
| 2493387 |
Novel cytotoxic peptides from the tropical marine cyanobacterium Hormothamnion enteromorphoides. 1. Discovery, isolation and initial chemical and biological characterization of the hormothamnins from wild and cultured material |
10.1007/BF01954842. |
Experientia |
Novel cytotoxic peptides from the tropical marine cyanobacterium Hormothamnion enteromorphoides. 1. Discovery, isolation and initial chemical and biological characterization of the hormothamnins from wild and cultured material
Abstract
- A Caribbean cyanobacterium, Hormothamnion enteromorphoides, was found to produce a complex mixture of ichthyotoxic peptides, perhaps explaining the apparent absence of predation upon these potentially palatable life forms. Bioassay-guided fractionation was used to isolate these toxic and antimicrobial natural products, and a variety of techniques including HR FAB mass spectrometry, 2D-NMR, traditional hydrolysis-amino acid analysis, and several chemical reactions were used to define the basic structural features of the major peptide, hormothamnin A. Hormothamnin A is a cyclic undecapeptide containing six common and five uncommon or new amino acid residues. HPLC analyses indicate that the relative proportions of these peptide natural products remain relatively constant between different collection locations and years, however, they do vary seasonally. Clonal isolates of this cyanobacterium in culture produce the full spectrum of toxic peptides.
|
| 2498262 |
Leukocytosis in mice following therapy with a novel antitumor agent, RA-700 |
10.1111/j.1349-7006.1989.tb02307.x. |
Jpn J Cancer Res |
Leukocytosis in mice following therapy with a novel antitumor agent, RA-700
Abstract
- Nine daily intravenous (iv) injections of RA-700 (an antitumor cyclic hexapeptide) at doses of 2 to 6 mg/kg/day caused increases of WBC counts at 4-6 days after treatment in normal C57BL/6 X DBA/2 (BDF1) mice. The percentages of neutrophils and lymphocytes were modified. There was a decrease of colony-forming units in culture (CFUc) in bone marrow to 40% of the control value on day 1 but CFUc rapidly returned to normal values on day 3. The colony-forming units in spleen (CFUs) in bone marrow decreased during treatment. On the other hand, CFUc and CFUs in spleen were increased from the initiation of treatment to the time prior to the increase of WBC count. Spleen weight increased after treatment, and histologically, increases of immature and also mature granulocytes and megakaryocytes were observed. However, RA-700 did not stimulate the progress of hematoprogenitors in vitro. The results indicated that RA-700 stimulates the progress of hematoprogenitors in the spleen, but this effect is probably indirect.
|
| 2501837 |
Bactericidal and bacteriolytic action of peptide antibiotic AS-48 against gram-positive and gram-negative bacteria and other organisms |
10.1016/0923-2508(89)90060-0. |
Res Microbiol |
Bactericidal and bacteriolytic action of peptide antibiotic AS-48 against gram-positive and gram-negative bacteria and other organisms
Abstract
- A purified peptide antibiotic AS-48 from Streptococcus faecalis spp liquiefaciens S-48 exerted a bactericidal mode of action against most Gram-positive and many Gram-negative bacteria tested. In many Gram-positive bacteria and the two Myxococcus species assayed, a bacteriolytic effect, as a consequence of primary lesions, was also observed. In general, the Gram-negative bacteria were more resistant to AS-48. Escherichia coli protoplasts showed increased sensitivity and those of a resistant yeast. Saccharomyces cerevisiae 3.2, became sensitive. These data suggest that resistance is related to the cell wall structure. AS-48 adsorbed rapidly to cell walls and cytoplasmic membranes of sensitive and resistant cells. Adsorption to cytoplasmic membranes involved complete neutralization of AS-48.
|
| 2506678 |
The effects of single L-amino acid substitutions on the lethal potencies of the microcystins |
10.1016/0041-0101(89)90051-2. |
Toxicon |
The effects of single L-amino acid substitutions on the lethal potencies of the microcystins
Abstract
- Microcystin-LR and -LA are more toxic than microcystin-LY and -RR in adult mice. They induce different degrees of thrombocytopenia and leukopenia, and the lethalities of their binary and ternary mixtures are addictive. Postnatal mice are resistant to doses of microcystin-LR that are lethal to adults but they are susceptible to higher doses. Substitution of a single L-amino acid for another in a microcystin markedly affects the dosimetric potency, but not the pathophysiology of its toxicity.
|
| 2508270 |
Structure and toxicity of a peptide hepatotoxin from the cyanobacterium Oscillatoria agardhii |
10.1016/0041-0101(89)90153-0. |
Toxicon |
Structure and toxicity of a peptide hepatotoxin from the cyanobacterium Oscillatoria agardhii
Abstract
- A peptide hepatotoxin was isolated by reversed phase liquid chromatography from the cyanobacterium Oscillatoria agardhii and characterized structurally and toxicologically. Amino acid analyses, proton nuclear magnetic resonance and fast atom bombardment mass spectrometry showed that the toxin is a cyclic heptapeptide (mol. wt 1023.5) with the structure cyclo-(Ala-Arg-Asp-Arg-Adda-Glu-N-methyldehydroAla) (Adda: 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid). In mice the toxic effects were restricted mainly to the liver where the toxin induced massive hemorrhages and a disruption of the lobular and sinusoidal structure. The i.p. LD50 of the toxin was 250 micrograms/kg. The structural and toxic properties of this peptide are very close to those of microcystins, cyclic peptide toxins produced by the cyanobacterium Microcystis aeruginosa.
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