Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycoprotein (GP) IIIb (also termed GPIV or CD36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. PAS-IV is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. The N-terminal sequence of PAS-IV is nearly identical to that of GPIIIb and monospecific anti-PAS-IV antibody reacts with GPIIIb, indicating that PAS-IV is structurally related to GPIIIb. In this study, human platelet GPIIIb and bovine epithelial PAS-IV were compared in terms of structural, immunologic, and functional characteristics. The two-dimensional tryptic peptide map of both intact and deglycosylated PAS-IV was highly similar but not identical to that of GPIIIb. PAS-IV and GPIIIb reacted to an equal extent with monoclonal antibodies OKM5 and OKM8 by enzyme-linked immunosorbent assay. GPIIIb bound to surface immobilized thrombospondin (TSP) in a concentration-dependent and saturable manner, with approximately 60% reduction in binding in the presence of EDTA. PAS-IV bound to TSP with similar characteristics except that maximum binding was consistently approximately 50% of that of GPIIIb and binding was not inhibited by EDTA. GPIIIb supported adhesion of Plasmodium falciparum-infected erythrocytes (PRBC) in a dose-dependent manner while no significant adhesion of PRBC to PAS-IV was observed. Our data demonstrate that while epithelial PAS-IV and platelet GPIIIb are structurally and immunologically related, there are significant differences in their functional properties. Whether this result is due to different posttranslational glycosylation modifications or that PAS-IV and GPIIIb represent a family of related cell adhesive protein receptors remains to be determined.
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PMID:Epithelial membrane glycoprotein PAS-IV is related to platelet glycoprotein IIIb binding to thrombospondin but not to malaria-infected erythrocytes. 171 May 15

A Plasmodium falciparum cDNA clone was isolated of which the insert is transcribed at high rates as a 1.4-kb mRNA in the sexual stages of the malaria parasite. The cDNA clone contains a copy of a non-interrupted gene which codes for a protein of 157 amino acids (Mr = 16607). This 16-kDa protein does not contain repetitive sequences and is characterised by a putative N-terminal signal sequence, a hydrophobic membrane anchor sequence and a highly hydrophilic C-terminal region suggesting that it is an integral membrane protein. Rabbit antisera raised against a synthetic peptide covering amino acids 31-47 of the 16-kDa protein and against recombinant fusion proteins recognised the 16-kDa antigen in protein extracts of gametocytes, macrogamete/zygotes and sporozoites by Western blot analysis. The rabbit antisera also reacted with gametes, gametocytes and sporozoites in a standard immunofluorescence assay. By immunoelectron microscopy using the protein A-gold method the 16-kDa protein could be clearly visualised on the surface of macrogametes and sporozoites, whereas the antigen was not detectable in the asexual erythrocytic stages of the parasite. The 16-kDa antigen of P. falciparum therefore might have the potential to elicit a dual protective immune response against the sporozoite and sexual stage parasites.
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PMID:A novel protein antigen of the malaria parasite Plasmodium falciparum, located on the surface of gametes and sporozoites. 203 55

There is a high prevalence of the erythrocyte polymorphism ovalocytosis associated with reduced susceptibility to malaria in Papua New Guinea. The major erythrocyte integral membrane protein, Band-3, showed markedly increased phosphorylation in whole cells or isolated ghosts from ovalocytic individuals. The cytoplasmic domain of the ovalocyte Band-3 was found to be approx. 3 kDa larger than the normocytic protein. The N-terminal sequence of the ovalocytic Band-3 was different from the reported sequence for human Band-3, suggesting that the increased size results from an N-terminal extension. Since this is the region of Band-3 which is phosphorylated and interacts with the red cell cytoskeleton, it is likely that this alteration in ovalocytic Band-3 is the underlying cause of the diverse alterations in ovalocytic cells including increased phosphorylation, increased membrane rigidity, decreased agglutinability by blood group antibodies and refractoriness to invasion by malarial parasites.
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PMID:Human erythrocyte Band-3 has an altered N terminus in malaria-resistant Melanesian ovalocytosis. 226 83

The rotavirus glycoprotein VP7 has a cleavable signal peptide and is normally resident as an integral membrane protein in the ER of infected cells. A gene was constructed in which the VP7 H2 signal peptide was replaced by one from influenza hemagglutinin. COS cells transfected with this gene produced VP7 with the correct amino terminus, but the protein was rapidly secreted. Uncleaved VP7 from either precursor was not detected in cells after brief pulse-labeling, suggesting that the signal peptide was not acting as a temporary anchor; rather, it exerted its effect despite rapid cleavage. By splicing the H2 signal peptide onto another reporter protein, the malaria S-antigen, we demonstrated that H2 was necessary, but not itself sufficient, for targeting and retention. We propose that an interaction between the cleaved signal peptide and other downstream sequences in VP7 is required for retention of this protein in the ER as an integral membrane polypeptide.
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PMID:The signal peptide of the rotavirus glycoprotein VP7 is essential for its retention in the ER as an integral membrane protein. 253 41

Duffy blood group antigenic epitopes are located on a 35-43 kD integral membrane protein of the erythrocyte membrane. This protein functions as a receptor for the human malaria parasite, Plasmodium vivax. The Duffy protein has been difficult to purify because of its tendency to form aggregates. Here we describe purification of a 28 kD tryptic fragment of the Duffy protein and purification of an 18 kD de-glycosylated form of the Duffy tryptic peptide using Thiopropyl Sepharose 6B chromatography and preparative SDS-PAGE. These Duffy-reactive peptides do not form aggregates and may prove amendable to protein sequencing.
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PMID:Purification of a 28 kD non-aggregating tryptic peptide of the Duffy blood group protein. 848 49

CD36 is an 88-kD integral membrane protein expressed on platelets, monocytes, macrophages, certain microvascular endothelia, and retinal pigment epithelium. It functions as an adhesive receptor for thrombospondin-1 (TSP-1), collagen, and malaria-infected erythrocytes and as a scavenger receptor for oxidized LDL and photoreceptor outer segments. The CD36-TSP-1 interaction plays a role in cell adhesion and the phagocytosis of apoptotic cells by macrophages. Because of the potential importance of the CD36-TSP-1 interaction in mediating atherogenic and inflammatory processes, we studied their expression in human peripheral blood monocytes exposed to soluble mediators known to regulate inflammation and atherogenesis. RNase protection assays showed 6- to 12-fold increases in CD36 mRNA in response to interleukin-4, monocyte colony-stimulating factor, and phorbol myristate acetate, while lipopolysaccharide and dexamethasone strongly downregulated CD36 mRNA. The downregulation of CD36 mRNA was associated with the disappearance of surface expression of CD36 antigen and loss of TSP-1 surface-binding capacity. Upregulation of CD36 mRNA was associated with a modest increase in surface antigen expression and a larger expansion of an intracellular pool of CD36. As with CD36, monocytes treated with monocyte colony-stimulating factor showed a rapid increase in TSP-1 mRNA expression. Moreover, while dexamethasone treatment decreased CD36 expression, it resulted in a rapid increase in TSP-1 mRNA, and while PMA increased CD36 mRNA, it rapidly decreased TSP-1 expression. Interferon gamma, which had no effect on CD36 mRNA, rapidly increased steady-state TSP-1 mRNA. Thus, expression of both CD36 and its ligand TSP-1 is regulated by soluble mediators, although certain mediators induce concordant changes and others discordant changes.
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PMID:Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. 869 41

The invasion of host red blood cells by Plasmodium falciparum merozoites is a complex process requiring multiple receptor-ligand interactions. Glycophorin A, a sialic acid-rich integral membrane protein, is an important RBC receptor for merozoites. We stably expressed glycophorin A in wild type Chinese hamster ovary (CHO) cells and in Lec 2 CHO cells which have a defect in the ability to sialylate proteins. Malaria merozoites were assessed for the ability to adhere to CHO cells that were either untransfected or expressed recombinant glycophorin A. Merozoites only adhered to wild type CHO cells and they did so irrespective of the expression of glycophorin A. These results suggest that cellular adhesion, the earliest event in the malaria invasion process, is mediated by sialic acid residues. This model system will provide valuable molecular information regarding early events in the malaria invasion process.
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PMID:Plasmodium falciparum merozoite adhesion is mediated by sialic acid. 878 Jun 81

Merozoite surface protein 4 (MSP4) of Plasmodium falciparum is a glycosylphosphatidylinositol-anchored integral membrane protein of 272 residues that possesses a single epidermal growth factor (EGF)-like domain near the carboxyl terminus. We have expressed both full-length MSP4 and a number of fragments in Escherichia coli and have used these recombinant proteins to raise experimental antisera. All recombinant proteins elicited specific antibodies that reacted with parasite-derived MSP4 by immunoblotting. Antibody reactivity was highly dependent on the protein conformation. For example, reduction and alkylation of MSP4 almost completely abolished the reactivity of several antibody preparations, including specificities directed to regions of the protein that do not contain cysteine residues and are far removed from the cysteine-containing EGF-like domain. This indicated the presence of conformation-dependent epitopes in MSP4 and demonstrated that proper folding of the EGF-like domain influenced the antigenicity of the entire molecule. The recombinant proteins were used to map epitopes recognized by individuals living in areas where malaria is endemic, and at least four distinct regions are naturally antigenic during infection. Binding of human antibodies to the EGF-like domain was essentially abrogated after reduction of the recombinant protein, indicating the recognition of conformational epitopes by the human immune responses. This observation led us to examine the importance of conformation dependence in responses to other integral membrane proteins of asexual stages. We analyzed the natural immune responses to a subset of these antigens and demonstrated that there is diminished reactivity to several antigens after reduction. These studies demonstrate the importance of reduction-sensitive structures in the maintenance of the antigenicity of several asexual-stage antigens and in particular the importance of the EGF-like domain in the antigenicity of MSP4.
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PMID:Structural and antigenic properties of merozoite surface protein 4 of Plasmodium falciparum. 1022 74

Erythrocyte invasion by the malaria merozoite requires the activity of merozoite proteases. We have previously identified a Plasmodium falciparum protein belonging to the superfamily of subtilisin-like serine proteases, which is expressed in a subset of secretory organelles in free merozoites. Here we describe the identification of a second P. falciparum subtilisin-like merozoite protein. Called PfSUB-2, it is encoded by a single copy gene and is expressed as a large putative type I integral membrane protein which undergoes extensive post-translational processing. The terminal processing product is expressed in an apical location in merozoites. PfSUB-2 may mediate one or more of the serine protease activities known to be associated with erythrocyte invasion.
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PMID:PfSUB-2: a second subtilisin-like protein in Plasmodium falciparum merozoites. 1055 62

Antibodies from hyperimmune monkey sera, selected by absorption to Plasmodium falciparum-infected erythrocytes, and elution at acidic pH, allowed us to characterize a novel parasite protein, Pfsbp1 (P. falciparum skeleton binding protein 1). Pfsbp1 is an integral membrane protein of parasite-induced membranous structures associated with the erythrocyte plasma membrane and referred to as Maurer's clefts. The carboxy-terminal domain of Pfsbp1, exposed within the cytoplasm of the host cell, interacts with a 35 kDa erythrocyte skeletal protein and might participate in the binding of the Maurer's clefts to the erythrocyte submembrane skeleton. Antibodies to the carboxy- and amino-terminal domains of Pfsbp1 labelled similar vesicular structures in the cytoplasm of Plasmodium chabaudi and Plasmodium berghei-infected murine erythrocytes, suggesting that the protein is conserved among malaria species, consistent with an important role of Maurer's cleft-like structures in the intraerythrocytic development of malaria parasites.
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PMID:Pfsbp1, a Maurer's cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton. 1108 21


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