Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites
Journal Title
Scientific Reports
Publication Type
Journal Article
Abstract
Central to the pathogenesis of malaria is the proliferation of Plasmodium falciparum parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood-stage vaccine and previous work indicates that phosphorylation of its cytoplasmic domain (CPD) is important to its function during invasion. Here we investigate the significance of each of the six available phospho-sites in the CPD. We confirm that the cyclic AMP/protein kinase A (PKA) signalling pathway elicits a phospho-priming step upon serine 610 (S610), which enables subsequent phosphorylation in vitro of a conserved, downstream threonine residue (T613) by glycogen synthase kinase 3 (GSK3). Both phosphorylation steps are required for AMA1 to function efficiently during invasion. This provides the first evidence that the functions of key invasion ligands of the malaria parasite are regulated by sequential phosphorylation steps.
Publisher
Springer Nature
WEHI Research Division(s)
Chemical Biology
PubMed ID
27698395
Publisher's Version
https://doi.org/10.1038/srep34479
Open Access at Publisher's Site
http://www.nature.com/articles/srep34479
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-10-19 11:52:33
Last Modified: 2016-10-19 12:55:18
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