The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins to Aldolase Is Enhanced by Phosphorylation
| Autor: | Munira Grainger, Suraya A. Diaz, Anthony A. Holder, Stephen R. Martin, Judith L. Green, Robert W. Moon, Steven Howell |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Plasmodium Erythrocytes malaria parasite invasion Cell Membranes Protozoan Proteins lcsh:Medicine cytoplasmic domain Synthetic Biotechnology Biochemistry Animal Cells Red Blood Cells Fructose-Bisphosphate Aldolase Post-Translational Modification Phosphorylation lcsh:Science Multidisciplinary actin polymerization merozoite proteins host-cell invasion Ligand (biochemistry) 3. Good health Engineering and Technology Synthetic Biology Cellular Structures and Organelles Cellular Types Research Article Biotechnology Protein Binding Protein family Recombinant Fusion Proteins Motor Proteins Green Fluorescent Proteins Plasmodium falciparum 030106 microbiology anonymous protein Biology Microbiology Binding Competitive 03 medical and health sciences motor complex Protein Domains Molecular Motors Virology Parasite Groups toxoplasma-gondii Animals Parasites Synthetic Peptides Apical membrane antigen 1 Binding site Protein kinase A Blood Cells Merozoites Host Cells Aldolase A lcsh:R Biology and Life Sciences Proteins Membrane Proteins Cell Biology Kinetics Interferometry 030104 developmental biology apicomplexan parasites Membrane protein biology.protein gliding motility Parasitology lcsh:Q Peptides Apicomplexa Viral Transmission and Infection |
| Zdroj: | PLoS ONE, Vol 11, Iss 9, p e0161850 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Aldolase has been implicated as a protein coupling the actomyosin motor and cell surface adhesins involved in motility and host cell invasion in the human malaria parasite Plasmodium falciparum. It binds to the cytoplasmic domain (CTD) of type 1 membrane proteins of the thrombospondin-related anonymous protein (TRAP) family. Other type 1 membrane proteins located in the apical organelles of merozoites, the form of the parasite that invades red blood cells, including apical membrane antigen 1 (AMA1) and members of the erythrocyte binding ligand (EBL) and reticulocyte binding homologue (RH) protein families have been implicated in host cell binding and invasion. Using a direct binding method we confirm that TRAP and merozoite TRAP (MTRAP) bind aldolase and show that the interaction is mediated by more than just the C-terminal six amino acid residues identified previously. Single amino acid substitutions in the MTRAP CTD abolished binding to aldolase. The CTDs of AMA1 and members of the EBL and RH protein families also bound to aldolase. MTRAP competed with AMA1 and RH4 for binding to aldolase, indicating overlapping binding sites. MTRAP CTD was phosphorylated in vitro by both calcium dependent kinase 1 (CDPK1) and protein kinase A, and this modification increased the affinity of binding to aldolase by ten-fold. Phosphorylation of the CTD of members of the EBL and RH protein families also increased their affinity for aldolase in some cases. To examine whether or not MTRAP expressed in asexual blood stage parasites is phosphorylated, it was tagged with GFP, purified and analysed, however no phosphorylation was detected. We propose that CTD binding to aldolase may be dynamically modulated by phosphorylation, and there may be competition for aldolase binding between different CTDs. The use and efficiency of alternate invasion pathways may be determined by the affinity of adhesins and cell invasion proteins for aldolase, in addition to their host ligand specificity. |
| Databáze: | OpenAIRE |
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