Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei.

Abstract:

:The glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) of Trypanosoma brucei is the most abundant GPI-anchored protein expressed on any cell, and is an essential virulence factor. To determine what structural features affect efficient expression of VSG, we made a series of mutations in two VSGs. Inserting 18 amino acids, between the amino- and carboxy-terminal domains, reduced the expression of VSG 221 to about 3% of the wild-type level. When this insertion was combined with deletion of the single carboxy-terminal subdomain, expression was reduced a further three-fold. In VSG 117, which contains two carboxy-terminal subdomains, point mutation of the intervening N-glycosylation site reduced expression about 15-fold. Deleting the most carboxy-terminal subdomain and intervening region, including the N-glycosylation site, reduced expression to 15-20% of wild type VSG, and deletion of both subdomains reduced expression to <1%. Despite their low abundance, all VSG mutants were GPI anchored on the cell surface. Our results suggest that, for a protein to be efficiently displayed on the surface of bloodstream-form T. brucei, it is essential that it contains the conserved structural motifs of a T. brucei VSG. Serum resistance-associated protein (SRA), which confers human infectivity on T. brucei, strongly resembles a VSG deletion mutant. Expression of three epitope-tagged versions of SRA in T. brucei conferred total resistance to human serum. SRA possesses a canonical GPI signal sequence, but we were unable to obtain unequivocal evidence for the presence of a GPI anchor. SRA was not released during osmotic lysis, indicating that it is not GPI anchored on the cell surface.

journal_name

Mol Biochem Parasitol

authors

Wang J,Böhme U,Cross GA

doi

10.1016/s0166-6851(03)00055-0

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

135-45

issue

2

eissn

0166-6851

issn

1872-9428

pii

S0166685103000550

journal_volume

128

pub_type

杂志文章
  • Structural analysis of the acetaldehyde dehydrogenase activity of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a member of the ADHE enzyme family.

    abstract::The ADHE family of enzymes are bifunctional acetaldehyde dehydrogenase (ALDH)/alcohol dehydrogenase (ADH) enzymes that probably arose from the fusion of genes encoding separate ALDH and ADH enzymes. Here we have used the Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) enzyme as a prototype to analyze the struct...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2004.06.002

    authors: Chen M,Li E,Stanley SL Jr

    更新日期:2004-10-01 00:00:00

  • Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.

    abstract::To investigate whether the lysosomes of Trypanosoma brucei are capable of uptake of macromolecules after internalization by the cell, we used Triton WR-1339, a non-digestible macromolecular compound, which is known to cause a marked decrease in the density of hepatic lysosomes due to massive intralysosomal storage. In...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(82)90077-9

    authors: Opperdoes FR,Van Roy J

    更新日期:1982-09-01 00:00:00

  • The P-glycoprotein-related gene family in Leishmania.

    abstract::P-glycoprotein gene amplification has been described in several drug-resistant parasitic protozoa. The first P-glycoprotein related gene described in Leishmania was ltpgpA, a gene frequently amplified in arsenite resistant Leishmania. Hybridization experiments indicated that ltpgpA was part of a gene family. In additi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00156-1

    authors: Légaré D,Hettema E,Ouellette M

    更新日期:1994-11-01 00:00:00

  • A role for tertiary structure in the generation of antigenic diversity and molecular association of the Tams1 polypeptide in Theileria annulata.

    abstract::The major merozoite-piroplasm surface antigen (mMPSA) of Theileria annulata, Tams1, is known to be antigenically diverse. The possession of variable N-linked glycosylation sites and removal of monoclonal antibody 5E1 reactivity by mild periodate treatment suggested, previously, that divergent epitopes may be conferred...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(02)00078-6

    authors: Katzer F,McKellar S,Ferguson MA,d'Oliveira C,Shiels BR

    更新日期:2002-06-01 00:00:00

  • Biochemical analysis, gene structure and localization of the 24 kDa glutathione S-transferase from Onchocerca volvulus.

    abstract::Survival of Onchocerca volvulus, a pathogenic human filarial parasite, is likely to depend upon the detoxification activities of the glutathione S-transferases (GSTs). The 24 kDa O. volvulus GST, OvGST2, was expressed in a bacterial system and the recombinant protein was purified to homogeneity by affinity chromatogra...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(96)02660-6

    authors: Liebau E,Wildenburg G,Brophy PM,Walter RD,Henkle-Dührsen K

    更新日期:1996-09-01 00:00:00

  • Serological cross-reaction between high molecular weight proteins synthesized in blood schizonts of Plasmodium yoelii, Plasmodium chabaudi and Plasmodium falciparum.

    abstract::A 230 000 molecular weight (MW) Plasmodium yoelii protein, a 250 000 MW P. chabaudi protein and a 195 000 MW P. falciparum protein, identified using monoclonal antibodies, have similar characteristics, and have been implicated as protective antigens. In this study the serological relationship between these proteins wa...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(83)90096-8

    authors: Holder AA,Freeman RR,Newbold CI

    更新日期:1983-11-01 00:00:00

  • Characterization of a candidate gene for GP72, an insect stage-specific antigen of Trypanosoma cruzi.

    abstract::The Trypanosoma cruzi insect stage-specific antigen GP72 was purified from epimastigotes and the amino acid sequences of peptide fragments determined. Oligonucleotides derived from these data were used to amplify and clone a cDNA sequence, which was used to isolate a full-length gene. All the sequenced peptides were e...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(91)90129-t

    authors: Cooper R,Inverso JA,Espinosa M,Nogueira N,Cross GA

    更新日期:1991-11-01 00:00:00

  • Glycogen metabolism in Schistosoma mansoni worms after their isolation from the host.

    abstract::Adult Schistosoma mansoni worms rapidly degrade their endogenous glycogen stores immediately after isolation from the host. In NCTC 109 or in a diphasic culture medium the glycogen levels slowly recovered again after the initial decrease. The rapid degradation of glycogen could be prevented, even in a simple salt medi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(87)90156-3

    authors: Tielens AG,van den Bergh SG

    更新日期:1987-07-01 00:00:00

  • Electrophoretic analyses of myofibrillar proteins from the body wall muscles of Ascaris suum.

    abstract::A myofibrillar protein extract has been isolated from the muscle of Ascaris suum. Two-dimensional electrophoresis of this extract revealed that the myosin light chain 1 (ALC1) migrates as 3 components with approximate isoelectric points in the range of 5.3-5.6. The most acidic component of ALC1 appeared to be phosphor...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(81)90007-4

    authors: Srihari T,Wiehrer W,Pette D,Harris BG

    更新日期:1981-06-01 00:00:00

  • Population genetic analysis and sub-structuring in Babesia bovis.

    abstract::The tick-borne protozoan parasite, Babesia bovis is one of the causes of bovine babesiosis, an economically important disease of cattle in tropical and sub-tropical countries. Using the recently published genome sequence of the parasite, we developed a panel of eight mini- and micro-satellite markers and used these to...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.02.002

    authors: Simuunza M,Bilgic H,Karagenc T,Syakalima M,Shiels B,Tait A,Weir W

    更新日期:2011-06-01 00:00:00

  • Molecular biology of the hexokinase isoenzyme pattern that distinguishes pathogenic Entamoeba histolytica from nonpathogenic Entamoeba dispar.

    abstract::The electrophoretic patterns of hexokinase and phosphoglucomutase have been widely used to distinguish Entamoeba histolytica from Entamoeba dispar isolates. Although E. histolytica and E. dispar, previously called pathogenic and nonpathogenic Entamoeba histolytica, differ clearly in sequences of many homologous genes,...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(97)90008-6

    authors: Ortner S,Clark CG,Binder M,Scheiner O,Wiedermann G,Duchêne M

    更新日期:1997-05-01 00:00:00

  • Enhanced Ca2+ uptake by mouse erythrocytes in malarial (Plasmodium berghei) infection.

    abstract::Erythrocytes from Plasmodium berghei-infected mice on incubation either in plasma or artificial isotonic media showed an increase in uptake of 45Ca2+ compared with erythrocytes from uninfected mice. Infected cells (55% parasitaemia) incubated in plasma from normal or infected mice gave uptake rates of 9.8 and 8.1 nmol...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(83)90023-3

    authors: Krungkrai J,Yuthavong Y

    更新日期:1983-03-01 00:00:00

  • Expression differential of microsomal and cytosolic glutathione-S-transferases in Fasciola hepatica resistant at triclabendazole.

    abstract::In the present work, we evaluate in vitro the cytosolic and microsomal activity of glutathione-S-transferases in adults of Fasciola hepatica susceptible (Cullompton Strain) and resistant (Sligo Strain) to triclabendazole. The triclabendazole resistant (Sligo) fluke expressed significant major metabolic activity of glu...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.09.011

    authors: Scarcella S,Lamenza P,Virkel G,Solana H

    更新日期:2012-01-01 00:00:00

  • Purification and characterization of a novel sialidase found in procyclic culture forms of Trypanosoma brucei.

    abstract::A membrane-bound sialidase (EC 3.2.1.18) was found in procyclic trypomastigotes of Trypanosoma brucei. The mammalian stage bloodstream form, however, displayed no sialidase activity. This sialidase is an integral surface protein, linked to the membrane via a glycosylphosphatidylinositol anchor. After osmotic lysis and...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(92)90091-w

    authors: Engstler M,Reuter G,Schauer R

    更新日期:1992-08-01 00:00:00

  • The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1.

    abstract::Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are larg...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2017.06.002

    authors: Shakya B,Penn WD,Nakayasu ES,LaCount DJ

    更新日期:2017-09-01 00:00:00

  • Molecules on the surface of the Plasmodium falciparum infected erythrocyte and their role in malaria pathogenesis and immune evasion.

    abstract::The surface of the erythrocyte undergoes a number of modifications during infection by Plasmodium falciparum. These modifications are critical for pathogenesis of severe disease and the acquisition of host immunity through their role in interactions between the host and the parasite and in antigenic variation. Our kno...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审

    doi:10.1016/s0166-6851(01)00275-4

    authors: Craig A,Scherf A

    更新日期:2001-07-01 00:00:00

  • Characterization of the eg95 gene family in the G6 genotype of Echinococcus granulosus.

    abstract::Cystic echinococcosis in humans and livestock animals is caused by infection with the cestode parasite Echinococcus granulosus. A number of genotypes of the parasite (designated G1-G10) are known to exist, with the genotype cluster G1-G3 and genotype G6 being responsible for the majority of humans infections. A recomb...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2012.02.005

    authors: Alvarez Rojas CA,Gauci CG,Nolan MJ,Harandi MF,Lightowlers MW

    更新日期:2012-06-01 00:00:00

  • A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii.

    abstract::We have demonstrated that bradyzoites return to the tissue-cyst stage by a developmental pathway that is indistinguishable from that initiated by sporozoites. Mature bradyzoites, like sporozoites from oocysts, were non-proliferative as they contained uniform 1N DNA contents, and replication occurred only in parasites ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(03)00198-1

    authors: Radke JR,Guerini MN,Jerome M,White MW

    更新日期:2003-10-01 00:00:00

  • Characterization and localization of Plasmodium falciparum homolog of prokaryotic ClpQ/HslV protease.

    abstract::The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent threonine proteases present in eukaryotes and prokaryotes, respectively that control levels of key regulatory proteins in the cell. The orthologue of prokaryotic HslV protease in Plasmodium falciparum (PfHslV) is a novel drug...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2007.01.002

    authors: Ramasamy G,Gupta D,Mohmmed A,Chauhan VS

    更新日期:2007-04-01 00:00:00

  • Use of Giardia, which appears to have a single nucleotide-sugar transporter for UDP-GlcNAc, to identify the UDP-Glc transporter of Entamoeba.

    abstract::Nucleotide-sugar transporters (NSTs) transport activated sugars (e.g. UDP-GlcNAc) from the cytosol to the lumen of the endoplasmic reticulum or Golgi apparatus where they are used to make glycoproteins and glycolipids. UDP-Glc is an important component of the N-glycan-dependent quality control (QC) system for protein ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2008.01.004

    authors: Banerjee S,Cui J,Robbins PW,Samuelson J

    更新日期:2008-05-01 00:00:00

  • Ecdysteroid excretion by adult Hymenolepis diminuta in vitro.

    abstract::Both patent and prepatent adult Hymenolepis diminuta excreted 20-hydroxyecdysone into the culture medium when maintained in vitro. Patent worms also excreted ecdysone and comparatively large quantities of unidentified immunoreactive material of a relatively apolar nature. This latter material was shown to be depleted ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(87)90075-2

    authors: Mercer JG,Munn AE,Arme C,Rees HH

    更新日期:1987-12-01 00:00:00

  • Characterization of trafficking pathways and membrane genesis in malaria-infected erythrocytes.

    abstract::The origin of membraneous structures in the cytoplasm of human erythrocytes infected with the malaria parasite, Plasmodium falciparum, was determined by confocal fluorescence imaging microscopy. When infectious merozoites invaded erythrocytes labeled with the fluorescent, lipophilic, non-exchangeable molecules DiIC16 ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)90038-8

    authors: Pouvelle B,Gormley JA,Taraschi TF

    更新日期:1994-07-01 00:00:00

  • A Plasmodium falciparum isolate with a chromosome 9 deletion expresses a trypsin-resistant cytoadherence molecule.

    abstract::Sequestration of Plasmodium falciparum infected erythrocytes in the cerebral circulation is strongly implicated in the pathogenesis of cerebral malaria. From previous studies it was postulated that genes essential for cytoadherence were located on the right arm of chromosome 9 as P. falciparum isolates with a deletion...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)90092-2

    authors: Chaiyaroj SC,Coppel RL,Magowan C,Brown GV

    更新日期:1994-09-01 00:00:00

  • Role of 3'-untranslated regions in the regulation of hexose transporter mRNAs in Trypanosoma brucei.

    abstract::Trypanosoma brucei is a unicellular parasite that is transmitted from one mammalian host to the next by tsetse flies. The expression of many trypanosome genes is regulated during the life cycle but there is no evidence for developmental control of transcription by RNA polymerase II. T. brucei expresses at least two he...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(95)02503-0

    authors: Hotz HR,Lorenz P,Fischer R,Krieger S,Clayton C

    更新日期:1995-12-01 00:00:00

  • Divergent evolutionary constraints on mitochondrial and nuclear genomes of malaria parasites.

    abstract::Genetic variation among malaria parasites has important consequences with regard to drug resistance, pathogenicity, immunity, transmission, and speciation. In this regard, malaria parasites have been shown to display a high degree of inter- and intra-species genetic divergence. The nuclear genomes of Plasmodium falcip...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(98)00093-0

    authors: McIntosh MT,Srivastava R,Vaidya AB

    更新日期:1998-09-01 00:00:00

  • Gender biased differential alternative splicing patterns of the transcriptional cofactor CA150 gene in Schistosoma mansoni.

    abstract::The complex molecular systems involved in the process of sex-differentiation and fertility in Schistosoma mansoni have not yet been completely described. Using a 4608-element cDNA microarray, we have now determined 90 and 139 genes with significantly (q-value

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.07.002

    authors: DeMarco R,Oliveira KC,Venancio TM,Verjovski-Almeida S

    更新日期:2006-12-01 00:00:00

  • Trypanosoma brucei: the effect of glycerol on the anaerobic metabolism of glucose.

    abstract::Studies measuring the glycolytic intermediate and adenine nucleotide concentrations in Trypanosoma brucei metabolising glucose either aerobically or under conditions where glycerol-3-phosphate oxidase is inactive have shown the following: 1. Inhibition with 0.5 mM salicylhydroxamic acid (SHAM) accurately simulates ana...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(80)90032-8

    authors: Hammond DJ,Bowman IB

    更新日期:1980-12-01 00:00:00

  • Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum.

    abstract::Intraerythrocytic Plasmodium falciparum digests vast amounts of hemoglobin within an acidic food vacuole (FV). Four homologous aspartic proteases participate in hemoglobin degradation within the FV. Plasmepsin (PM) I and II are thought to initiate degradation of the native hemoglobin molecule. PM IV and histo-aspartic...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(03)00119-1

    authors: Banerjee R,Francis SE,Goldberg DE

    更新日期:2003-07-01 00:00:00

  • Patterns of polymorphism in genomic regions flanking three highly polymorphic surface antigens in Plasmodium falciparum.

    abstract::Many surface antigens of the human malaria parasite Plasmodium falciparum show extraordinary diversity, with different alleles being so divergent as to be unalignable in some coding regions. To better understand the population history and modes of selection on such loci, we sequenced genomic regions flanking the highl...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2007.12.004

    authors: Amodu OK,Hartl DL,Roy SW

    更新日期:2008-05-01 00:00:00

  • Identification and functional characterization of a member of the PUR-alpha family from Schistosoma mansoni.

    abstract::Schistosoma mansoni p14 gene encodes an eggshell precursor that is expressed only in vitelline cells of mature female worms in response to a male stimulus. The upstream region of the p14 gene contains several potential cis-acting regulatory sequences. We used the upstream region of the p14 gene as bait in a yeast-one-...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(00)00292-9

    authors: Fantappie MR,Osman A,Niles EG,LoVerde PT

    更新日期:2000-10-01 00:00:00