Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity.
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Deletion of the region II adhesive motif from CSP abolished sporozoite gliding motility and severely impaired invasion of mosquito salivary glands and infection of the vertebrate host, whereas deletion of region I had no detectable phenotype.
"Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host."
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P. falciparum CSP is functional when substituted for the endogenous CSP of P. berghei, validating the transgenic complementation design used to assign these phenotypes to PfCSP.
"We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host."
Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum.
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The surface coat of extracellular P. falciparum stages consists largely of GPI-anchored plasma membrane proteins, the class to which CSP belongs.
"Most proteins that coat the surface of the extracellular forms of the human malaria parasite Plasmodium falciparum are attached to the plasma membrane via glycosylphosphatidylinositol (GPI) anchors."
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The proteomic part of the study was restricted to blood-stage parasites, and the eleven GPI anchors validated by radiolabelling are merozoite-stage surface proteins; CSP enters the study through the genome-wide GPI-HMM prediction.
"Focusing on the clinically relevant blood stage of the life cycle, proteomic analysis of proteins labeled with radioactive glucosamine identified GPI anchoring on 11 proteins (merozoite surface protein (MSP)-1, -2, -4, -5, -10, rhoptry-associated membrane antigen, apical sushi protein, Pf92, Pf38, Pf12, and Pf34)."
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein.
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PfCSP coats the sporozoite surface and is required for migration out of the skin, entry into the liver parenchyma and invasion of hepatocytes.
"which coats the PfSPZ surface and plays a key role in parasite migration out of the skin, entry into the liver parenchyma and invasion of hepatocytes7–12."
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Antibodies against PfCSP inhibit sporozoite traversal and invasion of a human hepatocyte cell line in vitro and reduce liver burden in a humanized-liver mouse model by up to 98.3%, demonstrating that CSP function is required for hepatocyte infection.
"Some antibodies, such as MGG3, MGG4, MGH2, MGU10 and MGU12, were very potent in reducing liver burden by up to 98.3%, while others, such as MGG8, MGH1, MGH3 and MGU1, were less effective (Fig. 2c)."
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Region I (KLKQP) of PfCSP is involved in N-terminal cleavage that permits sporozoite invasion of hepatocytes.
"region I (KLKQP) of PfCSP, which is involved in the cleavage of the N-terminus to allow PfSPZ invasion of hepatocytes"
Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein.
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PfCSP is GPI-anchored on the sporozoite surface and is critical for sporozoite development, motility and hepatocyte invasion.
"PfCSP is GPI-anchored on the sporozoite surface and plays a critical role in sporozoite development, motility and hepatocyte invasion [12, 13]."
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Passive transfer of anti-PfCSP monoclonal antibodies reduced parasite liver burden by more than 90% in vivo, consistent with a requirement for CSP in liver infection.
"Both antibodies are potent, especially at high concentrations (300 and 600 μg/mouse) with >90% reduction in liver burden load as compared to naïve infected mice (Fig 5)."
Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes.
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The hepatocyte receptors for CSP region II-plus are heparan sulfate proteoglycans on the basolateral plasma membrane, and recognition occurs through their glycosaminoglycan chains.
"We have now identified these receptors as heparan sulfate proteoglycans (HSPG). The binding of CS to the receptors is abolished by heparitinase treatment, indicating that the recognition of region II-plus is via the glycosaminoglycan chains."
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The CSP-binding proteoglycans are large (400-700 kDa), tightly membrane associated and released by mild trypsinization, properties shared with syndecans.
"They have a molecular weight of 400,000-700,000, are tightly associated with the plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the syndecan family of proteoglycans."
UniProtKB entry Q7K740 (CSP_PLAF7), circumsporozoite protein, Plasmodium falciparum 3D7
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CSP is a GPI-anchored cell membrane protein that is also cytoplasmic in developing oocysts before redistributing over the surface of the sporoblast and budding sporozoites.
"Localizes to the cytoplasm and the"
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During host cell invasion CSP is proteolytically cleaved at region I by a parasite papain-like cysteine protease, triggered by contact with highly sulfated host heparan sulfate proteoglycans; cleavage is required for productive invasion but not for adhesion.
"proteolytically cleaved at the cell membrane in the region I by a papain-like cysteine protease of parasite origin"