Proteins on the surface of the malaria parasite and cell invasion

Parasitology ◽  
1994 ◽  
Vol 108 (S1) ◽  
pp. S5-S18 ◽  
Author(s):  
A. A. Holder
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Cell Types ◽  
Merozoite Surface Protein ◽  
Amino Acid Sequences ◽  
Specific Cell ◽  
Binding Studies ◽  
Erythrocyte Invasion

SUMMARYThe malaria parasite exists in an extracellular form at several stages in its life cycle. Within the vertebrate host, sporozoites and merozoites have to invade specific cell types. Proteins on the surface of the parasite or externalized from specialized organelles have been implicated as ligands for receptors on the host cell surface. Direct binding studies have identified parasite proteins that interact with the target cell surface. Examination of the deduced amino acid sequences has allowed the identification of primary structural motifs which may have roles in this process. On the sporozoite, the circum-sporozoite protein and sporozoite surface protein-2, a protein initially located within micronemes, have been found to contain an amino acid sequence thought to be involved in mediating recognition of sulphated polysaccharides on the surface of a liver cell. On the merozoite, merozoite surface protein-1 may be involved in the initial recognition of red blood cells; this protein undergoes a complex series of modifications in the time between its synthesis as a precursor molecule and successful erythrocyte invasion. Other merozoite proteins located at the apical end of the parasite have been identified as erythrocyte or reticulocyte binding proteins.

scholarly journals Inhibition of Erythrocyte Invasion and Plasmodium falciparum Merozoite Surface Protein 1 Processing by Human Immunoglobulin G1 (IgG1) and IgG3 Antibodies

2009 ◽  
Vol 77 (12) ◽  
pp. 5659-5667 ◽  
Author(s):  
Maria Lazarou ◽  
José A. Guevara Patiño ◽  
Richard M. Jennings ◽  
Richard S. McIntosh ◽  
Jianguo Shi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dna Sequences ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Amino Acid Sequences ◽  
Human Immunoglobulin ◽  
Human Neutrophils ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Invasion ◽  
Carboxy Terminal

ABSTRACT Antigen-specific antibodies (Abs) to the 19-kDa carboxy-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP119) play an important role in protective immunity to malaria. Mouse monoclonal Abs (MAbs) 12.10 and 12.8 recognizing MSP119 can inhibit red cell invasion by interfering with MSP1 processing on the merozoite surface. We show here that this ability is dependent on the intact Ab since Fab and F(ab′)2 fragments derived from MAb 12.10, although capable of binding MSP1 with high affinity and competing with the intact antibody for binding to MSP1, were unable to inhibit erythrocyte invasion or MSP1 processing. The DNA sequences of the variable (V) regions of both MAbs 12.8 and 12.10 were obtained, and partial amino acid sequences of the same regions were confirmed by mass spectrometry. Human chimeric Abs constructed by using these sequences, which combine the original mouse V regions with human γ1 and γ3 constant regions, retain the ability to bind to both parasites and recombinant MSP119, and both chimeric human immunoglobulin G1s (IgG1s) were at least as good at inhibiting erythrocyte invasion as the parental murine MAbs 12.8 and 12.10. Furthermore, the human chimeric Abs of the IgG1 class (but not the corresponding human IgG3), induced significant NADPH-mediated oxidative bursts and degranulation from human neutrophils. These chimeric human Abs will enable investigators to examine the role of human Fcγ receptors in immunity to malaria using a transgenic parasite and mouse model and may prove useful in humans for neutralizing parasites as an adjunct to antimalarial drug therapy.

scholarly journals Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein.

1994 ◽  
Vol 180 (1) ◽  
pp. 389-393 ◽  
Author(s):  
M J Blackman ◽  
T J Scott-Finnigan ◽  
S Shai ◽  
A A Holder
Keyword(s):  
Malaria Parasite ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Secondary Processing ◽  
Erythrocyte Invasion ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Protective Antibodies ◽  
Epidermal Growth ◽  
Membrane Bound

When merozoites of the malaria parasite Plasmodium falciparum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be sufficient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.

scholarly journals Neogenin, an avian cell surface protein expressed during terminal neuronal differentiation, is closely related to the human tumor suppressor molecule deleted in colorectal cancer.

1994 ◽  
Vol 127 (6) ◽  
pp. 2009-2020 ◽  
Author(s):  
J Vielmetter ◽  
J F Kayyem ◽  
J M Roman ◽  
W J Dreyer
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Terminal Differentiation ◽  
Human Tumor ◽  
Surface Protein ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Surface Protein ◽  
Deleted In Colorectal Cancer ◽  
Ig Superfamily

Using a monoclonal antibody, we have identified and characterized a previously unknown cell surface protein in chicken that we call neogenin and have determined its primary sequence. The deduced amino acid sequence and structure of neogenin characterize it as a member of the immunoglobulin (Ig) superfamily. Based on amino acid sequence similarities, neogenin is closely related to the human tumor suppressor molecule DCC (deleted in colorectal cancer). Neogenin and DCC define a subgroup of Ig superfamily proteins structurally distinct from other Ig molecules such as N-CAM, Ng-CAM, and Bravo/Nr-CAM. As revealed by antibody staining of tissue sections and Western blots, neogenin expression correlates with the onset of neuronal differentiation. Neogenin is also found on cells in the lower gastrointestinal tract of embryonic chickens. DCC has been observed in human neural tissues and has been shown to be essential for terminal differentiation of specific cell types in the adult human colon. These parallels suggest that neogenin, like DCC, is functionally involved in the transition from cell proliferation to terminal differentiation of specific cell types. Since neogenin is expressed on growing neurites and downregulated at termination of neurite growth, it may also play an important role in many of the complex functional aspects of neurite extension and intercellular signaling.

scholarly journals Molecular Genetic Characterization of the Merozoite Surface Protein 1 Gene of Plasmodium vivax from Reemerging Korean Isolates

2009 ◽  
Vol 16 (5) ◽  
pp. 733-738 ◽  
Author(s):  
So-Hee Kim ◽  
Seung-Young Hwang ◽  
Jeong Hwan Shin ◽  
Chi-Sook Moon ◽  
Dong-Wook Kim ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasmodium Vivax ◽  
Molecular Genetic ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Amino Acid Sequences ◽  
Merozoite Surface Protein 1 ◽  
Almost All ◽  
Molecular Genetic Characterization

ABSTRACT Plasmodium vivax merozoite surface protein 1 (PvMSP-1) has been considered a major candidate for the development of an antimalaria vaccine, but the molecule exhibits antigenic diversity among isolates. The extent of genetic polymorphism in the region between interspecies conserved blocks 4 and 5 (ICB4 and ICB5) of the PvMSP-1 gene was analyzed for 30 Korean isolates. Two genotypes, SK-A and SK-B, were identified on the basis of amino acid substitution. Almost all the amino acid sequences of the Korean isolates were nearly identical to those of the Solomon Island isolate Solo-83 (97.8 to 99.9% similarity) and Philippine isolates Ph-79, Ph-52-2, and Ph-49 (97.3 to 99.8% similarity). Also, we report two sequences in the isolates that were characterized on the basis of restriction fragment length polymorphism (RFLP). The RFLP profiles following digestion with the DraI restriction enzyme produced two distinguishable patterns. This study might be the first report of the region between ICB4 and ICB5 of the MSP-1 gene of P. vivax in South Korea.

scholarly journals ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes

2014 ◽  
Vol 6 (247) ◽  
pp. 247ra103-247ra103 ◽  
Author(s):  
Siegfried Ussar ◽  
Kevin Y. Lee ◽  
Simon N. Dankel ◽  
Jeremie Boucher ◽  
Max-Felix Haering ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Cell Types ◽  
Amino Acid Transporter ◽  
Specific Cell ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Brown Adipocytes ◽  
Beige Adipocytes ◽  
Acid Transporter

White, beige, and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige, and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vitro, and in vivo methods, we have identified three new cell surface markers of adipose cell types. The amino acid transporter ASC-1 is a white adipocyte–specific cell surface protein, with little or no expression in brown adipocytes, whereas the amino acid transporter PAT2 and the purinergic receptor P2RX5 are cell surface markers expressed in classical brown and beige adipocytes in mice. These markers also selectively mark brown/beige and white adipocytes in human tissue. Thus, ASC-1, PAT2, and P2RX5 are membrane surface proteins that may serve as tools to identify and target white and brown/beige adipocytes for therapeutic purposes.

scholarly journals tANCHOR: a novel mammalian cell surface peptide display system

BioTechniques ◽  
2020 ◽  
Author(s):  
Daniel Ivanusic ◽  
Kazimierz Madela ◽  
Heidi Burghard ◽  
Gudrun Holland ◽  
Michael Laue ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Amino Acid Sequences ◽  
Display System ◽  
Extracellular Loop ◽  
Binding Studies ◽  
Small Proteins ◽  
Potential Applications ◽  
Large Extracellular Loop ◽  
Peptide Display

A novel tool for the presentation of peptides and small proteins on the surface of human cells has been developed. Our tANCHOR system utilizes tetraspanin anchors containing heterologous amino acid sequences inserted instead of the large extracellular loop. This technology allows a highly effective extracellular display of epitopes for antibody binding studies and many other potential applications.

scholarly journals Distinct Th1- and Th2-Type Prenatal Cytokine Responses to Plasmodium falciparum Erythrocyte Invasion Ligands

2005 ◽  
Vol 73 (6) ◽  
pp. 3462-3470 ◽  
Author(s):  
Indu Malhotra ◽  
Peter Mungai ◽  
Eric Muchiri ◽  
John Ouma ◽  
Shobhona Sharma ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cord Blood ◽  
Interleukin 2 ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Cd8 Cells ◽  
Erythrocyte Invasion ◽  
Cytokine Responses ◽  
Th1 And Th2 Responses ◽  
Th1 And Th2

ABSTRACT Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.

scholarly journals Cellular Receptors Involved in KSHV Infection

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 118
Author(s):  
Emma van der Meulen ◽  
Meg Anderton ◽  
Melissa J. Blumenthal ◽  
Georgia Schäfer
Keyword(s):  
Virus Infection ◽  
Cell Surface ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Cell Types ◽  
Target Cells ◽  
Specific Cell ◽  
Cellular Receptors ◽  
Diverse Range ◽  
Kshv Infection

The process of Kaposi’s Sarcoma Herpes Virus’ (KSHV) entry into target cells is complex and engages several viral glycoproteins which bind to a large range of host cell surface molecules. Receptors for KSHV include heparan sulphate proteoglycans (HSPGs), several integrins and Eph receptors, cystine/glutamate antiporter (xCT) and Dendritic Cell-Specific Intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This diverse range of potential binding and entry sites allows KSHV to have a broad cell tropism, and entry into specific cells is dependent on the available receptor repertoire. Several molecules involved in KSHV entry have been well characterized, particularly those postulated to be associated with KSHV-associated pathologies such as Kaposi’s Sarcoma (KS). In this review, KSHV infection of specific cell types pertinent to its pathogenesis will be comprehensively summarized with a focus on the specific cell surface binding and entry receptors KSHV exploits to gain access to a variety of cell types. Gaps in the current literature regarding understanding interactions between KSHV glycoproteins and cellular receptors in virus infection are identified which will lead to the development of virus infection intervention strategies.

Localization and expression of msp130, a primary mesenchyme lineage-specific cell surface protein in the sea urchin embryo

Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 255-265 ◽  
Author(s):  
J.A. Anstrom ◽  
J.E. Chin ◽  
D.S. Leaf ◽  
A.L. Parks ◽  
R.A. Raff
Keyword(s):  
Cell Surface ◽  
Sea Urchin ◽  
Sea Water ◽  
Surface Protein ◽  
Specific Cell ◽  
Cell Surface Protein ◽  
Sea Urchin Embryo ◽  
A Cell ◽  
Mesenchyme Cells ◽  
Primary Mesenchyme Cells

In this report, we use a monoclonal antibody (B2C2) and antibodies against a fusion protein (Leaf et al. 1987) to characterize msp130, a cell surface protein specific to the primary mesenchyme cells of the sea urchin embryo. This protein first appears on the surface of these cells upon ingression into the blastocoel. Immunoelectronmicroscopy shows that msp130 is present in the trans side of the Golgi apparatus and on the extracellular surface of primary mesenchyme cells. Four precursor proteins to msp130 are identified and we show that B2C2 recognizes only the mature form of msp130. We demonstrate that msp130 contains N-linked carbohydrate groups and that the B2C2 epitope is sensitive to endoglycosidase F digestion. Evidence that msp130 is apparently a sulphated glycoprotein is presented. The recognition of the B2C2 epitope of msp130 is disrupted when embryos are cultured in sulphate-free sea water. In addition, two-dimensional immunoblots show that msp130 is an acidic protein that becomes substantially less acidic in the absence of sulphate. We also show that two other independently derived monoclonal antibodies, IG8 (McClay et al. 1983; McClay, Matranga & Wessel, 1985) and 1223 (Carson et al. 1985), recognize msp130, and suggest this protein to be a major cell surface antigen of primary mesenchyme cells.

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