3D structure determination of STARP peptides implicated in P. falciparum invasion of hepatic cells
To block the different stages of Plasmodium falciparum invasion into human hepatocytes and red blood cells, we have focused on those proteins belonging to the pre-erythrocytic stage. One of these proteins is Sporozoite Threonine and Asparagine Rich Protein (STARP), which is a ligand used by P. falci...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2010 |
| País: | Colombia |
| Institución: | Universidad del Rosario |
| Repositorio: | Repositorio EdocUR - U. Rosario |
| Idioma: | inglés |
| OAI Identifier: | oai:repository.urosario.edu.co:10336/23458 |
| Acceso en línea: | https://doi.org/10.1016/j.vaccine.2010.05.025 https://repository.urosario.edu.co/handle/10336/23458 |
| Access Level: | acceso abierto |
| Palabra clave: | HLA DQB1 antigen Malaria vaccine Protozoal protein Sporozoite threonine and asparagine rich protein Unclassified drug HLA DR antigen HLA DRB1 antigen Parasite antigen Protein binding Protozoon antibody Alpha helix Amino acid sequence Animal experiment Animal model Aotus Article Circular dichroism Controlled study Drug structure Immunogenicity Nonhuman Nuclear Overhauser effect Peptide synthesis Plasmodium falciparum Priority journal Proton nuclear magnetic resonance Sporozoite Vaccine production Animal Antibody production Blood Chemistry Human Immunology Liver cell Malaria falciparum Molecular genetics Parasitology Pathogenicity Protein tertiary structure Amino Acid Sequence Animals Antibody Formation Aotus trivirgatus Hepatocytes HLA-DR Antigens Humans Malaria Vaccines Molecular Sequence Data Protein Binding HLA-DRB1 Chains 1H NMR Structure Falciparum Protozoan Tertiary STARP antigen Antibodies Antigens Malaria Protein Structure |
| Sumario: | To block the different stages of Plasmodium falciparum invasion into human hepatocytes and red blood cells, we have focused on those proteins belonging to the pre-erythrocytic stage. One of these proteins is Sporozoite Threonine and Asparagine Rich Protein (STARP), which is a ligand used by P. falciparum parasites to bind Hepatic cells (HepG2). Previous studies on this protein identified two conserved peptides binding with high activity to HepG2 cells (namely 20546 and 20570) with corresponding critical hepatic-cell binding residues and determined an important role for these two peptides in the invasion process. This study shows the results of immunization trials in Aotus monkeys with native STARP peptides and analogues modified in critical hepatic-cell binding residues. The results show that native peptides are not immunogenic but can induce high-antibody titers when their critical residues are replaced by other with similar volume and mass but different polarity. Nuclear Magnetic Resonance (1H NMR) studies revealed that native peptides (non-immunogenic) displayed shorter ?-helical regions compared to their highly immunogenic modified analogues. Binding assays with HLA-DR?1* molecules showed that 20546 modified peptides inducing high-antibody titers (24972, 24320 and 24486) bound to HLA-DR?1*0301 molecules, while the 20570 modified analogue (24322) bound to HLA-DR?1*0101. The results support including these high-immunogenic STARP-derived modified peptides as pre-erythrocytic candidates to be included in the design of a synthetic antimalarial vaccine. © 2010 Elsevier Ltd. |
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