A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

Abstract:

:Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.

authors

England BP,Balasubramanian P,Uings I,Bethell S,Chen MJ,Schatz PJ,Yin Q,Chen YF,Whitehorn EA,Tsavaler A,Martens CL,Barrett RW,McKinnon M

doi

10.1073/pnas.110053997

keywords:

subject

Has Abstract

pub_date

2000-06-06 00:00:00

pages

6862-7

issue

12

eissn

0027-8424

issn

1091-6490

pii

110053997

journal_volume

97

pub_type

杂志文章
  • The central cytoplasmic loop of the major facilitator superfamily of transport proteins governs efficient membrane insertion.

    abstract::Deletion of 5 residues (Delta5) from the central cytoplasmic loop of the lactose permease of Escherichia coli has no significant effect on expression or activity, whereas Delta12 leads to increased rates of permease turnover after membrane insertion and decreased transport activity, and Delta20 abolishes insertion and...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.140224497

    authors: Weinglass AB,Kaback HR

    更新日期:2000-08-01 00:00:00

  • The mouse histone H2a gene contains a small element that facilitates cytoplasmic accumulation of intronless gene transcripts and of unspliced HIV-1-related mRNAs.

    abstract::Histone mRNAs are naturally intronless and accumulate efficiently in the cytoplasm. To learn whether there are cis-acting sequences within histone genes that allow efficient cytoplasmic accumulation of RNAs, we made recombinant constructs in which sequences from the mouse H2a gene were cloned into a human beta-globin ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.19.10104

    authors: Huang Y,Carmichael GG

    更新日期:1997-09-16 00:00:00

  • Intracellular-pH dependence of Na-H exchange and acid loading in quiescent and arginine vasopressin-activated mesangial cells.

    abstract::We studied intracellular pH (pHi) regulation in the absence of HCO3- in single mesangial cells (MCs) with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(and -6)carboxyfluorescein. Our approach was to acid load the cells by an NH+4 prepulse and to monitor the subsequent pHi recovery. Previous work on MCs and other ce...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.15.5921

    authors: Boyarsky G,Ganz MB,Cragoe EJ Jr,Boron WF

    更新日期:1990-08-01 00:00:00

  • Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    abstract::Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec)....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1212759109

    authors: Breitkopf SB,Yuan M,Pihan GA,Asara JM

    更新日期:2012-10-02 00:00:00

  • Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1.

    abstract::Herpes simplex virus 1 (HSV-1) infection induces transcription of the chloramphenicol acetyltransferase (CAT) gene directed by the long terminal repeat (LTR) of human immunodeficiency virus (HIV) in both transiently and permanently transfected cells containing the HIV-LTR/CAT hybrid gene. To define the mechanism by wh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.21.7408

    authors: Mosca JD,Bednarik DP,Raj NB,Rosen CA,Sodroski JG,Haseltine WA,Hayward GS,Pitha PM

    更新日期:1987-11-01 00:00:00

  • Energy transport in peptide helices.

    abstract::We investigate energy transport through an alpha-aminoisobutyric acid-based 3(10)-helix dissolved in chloroform in a combined experimental-theoretical approach. Vibrational energy is locally deposited at the N terminus of the helix by ultrafast internal conversion of a covalently attached, electronically excited, azob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0701762104

    authors: Botan V,Backus EH,Pfister R,Moretto A,Crisma M,Toniolo C,Nguyen PH,Stock G,Hamm P

    更新日期:2007-07-31 00:00:00

  • Structural studies of viperin, an antiviral radical SAM enzyme.

    abstract::Viperin is an IFN-inducible radical S-adenosylmethionine (SAM) enzyme that inhibits viral replication. We determined crystal structures of an anaerobically prepared fragment of mouse viperin (residues 45-362) complexed with S-adenosylhomocysteine (SAH) or 5'-deoxyadenosine (5'-dAdo) and l-methionine (l-Met). Viperin c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1705402114

    authors: Fenwick MK,Li Y,Cresswell P,Modis Y,Ealick SE

    更新日期:2017-06-27 00:00:00

  • A model system to study genomic imprinting of human genes.

    abstract::Somatic-cell hybrids have been shown to maintain the correct epigenetic chromatin states to study developmental globin gene expression as well as gene expression on the active and inactive X chromosomes. This suggests the potential use of somatic-cell hybrids containing either a maternal or a paternal human chromosome...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.25.14857

    authors: Gabriel JM,Higgins MJ,Gebuhr TC,Shows TB,Saitoh S,Nicholls RD

    更新日期:1998-12-08 00:00:00

  • Genetics of somatic mammalian cells: demonstration of a human esterase activator gene linked to the adeB gene.

    abstract::Prototrophic hybrids formed from an adenine-requiring Chinese hamster cell and human fibroblasts uniformly display new esterase activity that differs from that of either parental cell in electrophoretic mobility and substrate specificity. The hybrids that grew in the selective medium and possessed the new esterase act...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.11.3273

    authors: Kao FT,Puck TT

    更新日期:1972-11-01 00:00:00

  • Apolipoprotein E and Alzheimer disease.

    abstract::Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown. Isoform-specific differences have been ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.92.11.4725

    authors: Strittmatter WJ,Roses AD

    更新日期:1995-05-23 00:00:00

  • Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis.

    abstract::Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907550106

    authors: Schonthaler HB,Huggenberger R,Wculek SK,Detmar M,Wagner EF

    更新日期:2009-12-15 00:00:00

  • Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages.

    abstract::Cryptococcus neoformans (Cn) is a soil fungus that causes life-threatening meningitis in immunocompromised patients and is a facultative intracellular pathogen capable of replication inside macrophages. The mechanism by which environmental fungi acquire and maintain virulence for mammalian hosts is unknown. We hypothe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.261418798

    authors: Steenbergen JN,Shuman HA,Casadevall A

    更新日期:2001-12-18 00:00:00

  • Myofibrillogenesis visualized in living embryonic cardiomyocytes.

    abstract::Myofibril formation was visualized in cultured live cardiomyocytes that were transfected with plasmids expressing green fluorescent protein (GFP) linked to the Z-band protein, alpha-actinin. The expression of this fluorescent protein provided an in vivo label for structures containing alpha-actinin. The GFP-alpha-acti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.17.9493

    authors: Dabiri GA,Turnacioglu KK,Sanger JM,Sanger JW

    更新日期:1997-08-19 00:00:00

  • Liposome-mediated delivery of tobacco mosaic virus RNA into tobacco protoplasts: A sensitive assay for monitoring liposome-protoplast interactions.

    abstract::Tobacco mosaic virus (TMV) RNA was encapsulated in large, unilamellar phospholipid vesicles (liposomes), and the encapsulated TMV RNA was shown to be infectious when incubated with tobacco protoplasts under appropriate conditions. Maximal virus production in protoplasts was observed after their incubation with TMV RNA...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.6.1859

    authors: Fraley RT,Dellaporta SL,Papahadjopoulos D

    更新日期:1982-03-01 00:00:00

  • Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein.

    abstract::The FKBP12-rapamycin-associated protein (FRAP; also called RAFT1/mTOR) regulates translation initiation and entry into the cell cycle. Depriving cells of amino acids or treating them with the small molecule rapamycin inhibits FRAP and results in rapid dephosphorylation and inactivation of the translational regulators ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.8.4438

    authors: Peterson RT,Desai BN,Hardwick JS,Schreiber SL

    更新日期:1999-04-13 00:00:00

  • Comparing the mechanism of water condensation and evaporation in glassy aerosol.

    abstract::Atmospheric models generally assume that aerosol particles are in equilibrium with the surrounding gas phase. However, recent observations that secondary organic aerosols can exist in a glassy state have highlighted the need to more fully understand the kinetic limitations that may control water partitioning in ambien...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1200691109

    authors: Bones DL,Reid JP,Lienhard DM,Krieger UK

    更新日期:2012-07-17 00:00:00

  • Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1.

    abstract::Metastatic colorectal cancer (mCRC) patients have poor overall survival despite using irinotecan- or oxaliplatin-based chemotherapy combined with anti-EGFR (epidermal growth factor receptor) drugs, especially those with the oncogene mutation of KRAS Metformin has been reported as a potentially novel antitumor agent in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1918845117

    authors: Xie J,Xia L,Xiang W,He W,Yin H,Wang F,Gao T,Qi W,Yang Z,Yang X,Zhou T,Gao G

    更新日期:2020-06-09 00:00:00

  • Transformation of follicular lymphoma to diffuse large-cell lymphoma: alternative patterns with increased or decreased expression of c-myc and its regulated genes.

    abstract::The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene-expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.132253599

    authors: Lossos IS,Alizadeh AA,Diehn M,Warnke R,Thorstenson Y,Oefner PJ,Brown PO,Botstein D,Levy R

    更新日期:2002-06-25 00:00:00

  • Conformational transitions in DNA polymerase I revealed by single-molecule FRET.

    abstract::The remarkable fidelity of most DNA polymerases depends on a series of early steps in the reaction pathway which allow the selection of the correct nucleotide substrate, while excluding all incorrect ones, before the enzyme is committed to the chemical step of nucleotide incorporation. The conformational transitions t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910909107

    authors: Santoso Y,Joyce CM,Potapova O,Le Reste L,Hohlbein J,Torella JP,Grindley ND,Kapanidis AN

    更新日期:2010-01-12 00:00:00

  • Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA.

    abstract::A cloned complementary DNA sequence has been isolated from a human placental cDNA library in the bacteriophage expression vector lambda gt11 after screening with polyclonal antibodies against human placental aromatase-system cytochrome P-450 (P-450Arom). A single recombinant clone, lambda hAROM1, was characterized by ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.17.6387

    authors: Evans CT,Ledesma DB,Schulz TZ,Simpson ER,Mendelson CR

    更新日期:1986-09-01 00:00:00

  • Experience sampling during fMRI reveals default network and executive system contributions to mind wandering.

    abstract::Although mind wandering occupies a large proportion of our waking life, its neural basis and relation to ongoing behavior remain controversial. We report an fMRI study that used experience sampling to provide an online measure of mind wandering during a concurrent task. Analyses focused on the interval of time immedia...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900234106

    authors: Christoff K,Gordon AM,Smallwood J,Smith R,Schooler JW

    更新日期:2009-05-26 00:00:00

  • Sugar demand, not auxin, is the initial regulator of apical dominance.

    abstract::For almost a century the plant hormone auxin has been central to theories on apical dominance, whereby the growing shoot tip suppresses the growth of the axillary buds below. According to the classic model, the auxin indole-3-acetic acid is produced in the shoot tip and transported down the stem, where it inhibits bud...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1322045111

    authors: Mason MG,Ross JJ,Babst BA,Wienclaw BN,Beveridge CA

    更新日期:2014-04-22 00:00:00

  • p53 accumulates but is functionally impaired when DNA synthesis is blocked.

    abstract::p53 is required for the induction of a G(1) and/or G(2) irreversible arrest after gamma irradiation (IR), whereas blocked DNA replication causes a p53-independent S-phase arrest. We have examined the response to p53 when DNA synthesis is blocked by hydroxyurea (HU) or aphidicolin or when DNA is damaged by gamma IR. Si...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.021282898

    authors: Gottifredi V,Shieh S,Taya Y,Prives C

    更新日期:2001-01-30 00:00:00

  • A note on statistical analysis of shape through triangulation of landmarks.

    abstract::In an earlier paper, the author jointly with S. Suryawanshi proposed statistical analysis of shape through triangulation of landmarks on objects. It was observed that the angles of the triangles are invariant to scaling, location, and rotation of objects. No distinction was made between an object and its reflection. T...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.7.2995

    authors: Rao CR

    更新日期:2000-03-28 00:00:00

  • Kinetics of hydrogen bond breakage in the process of unfolding of ribonuclease A measured by pulsed hydrogen exchange.

    abstract::A sensitive test for kinetic unfolding intermediates in ribonuclease A (EC 3.1.27.5) is performed under conditions where the enzyme unfolds slowly (10 degrees C, pH 8.0, 4.5 M guanidinium chloride). Exchange of peptide NH protons (2H-1H) is used to monitor structural opening of individual hydrogen bonds during unfoldi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.7.2657

    authors: Kiefhaber T,Baldwin RL

    更新日期:1995-03-28 00:00:00

  • Identification and characterization of amelogenin genes in monotremes, reptiles, and amphibians.

    abstract::Two features make the tooth an excellent model in the study of evolutionary innovations: the relative simplicity of its structure and the fact that the major tooth-forming genes have been identified in eutherian mammals. To understand the nature of the innovation at the molecular level, it is necessary to identify the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.13056

    authors: Toyosawa S,O'hUigin C,Figueroa F,Tichy H,Klein J

    更新日期:1998-10-27 00:00:00

  • Evolutionary and genetic implications of sequence variation in two nonallelic HLA-DR beta-chain cDNA sequences.

    abstract::Most HLA haplotypes carry two expressed DR beta-chain genes; in the DR4 haplotype, the polymorphic locus has been called DR beta 1 and the apparently nonpolymorphic locus has been called DR beta 2. We have isolated nearly full-length DR beta-chain cDNA clones representing each of these two loci from a cell line homozy...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.1.209

    authors: Curtsinger JM,Hilden JM,Cairns JS,Bach FH

    更新日期:1987-01-01 00:00:00

  • Anomalous and selective DNA mutations of the Old World monkey alpha-globin genes.

    abstract::It has been a widely accepted hypothesis that the molecular clock slows down during evolution of higher primates. By molecular cloning and nucleotide sequence comparison of a rhesus macaque alpha-globin gene to its homologs in man, orangutan, olive baboon, and other mammals, we demonstrate a burst of evolution of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.4.1312

    authors: Shaw JP,Marks J,Shen CC,Shen CK

    更新日期:1989-02-01 00:00:00

  • Generalizing Fisher's "reproductive value": "Incipient" and "penultimate" reproductive-value functions when environment limits growth; linear approximants for nonlinear Mendelian mating models.

    abstract::In the usual Darwinian case in which struggle for existence leads to density limitations on the environment's carrying capacity, R. A. Fisher's reproductive-value concept reduces to zero for every initial age group. To salvage some meaning for Fisher's notion, two variant reproductive-value concepts are defined here: ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.12.6327

    authors: Samuelson PA

    更新日期:1978-12-01 00:00:00

  • Selective translation by alternative bacterial ribosomes.

    abstract::Alternative ribosome subunit proteins are prevalent in the genomes of diverse bacterial species, but their functional significance is controversial. Attempts to study microbial ribosomal heterogeneity have mostly relied on comparing wild-type strains with mutants in which subunits have been deleted, but this approach ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2009607117

    authors: Chen YX,Xu ZY,Ge X,Sanyal S,Lu ZJ,Javid B

    更新日期:2020-08-11 00:00:00