title: Intrinsic disorder within the erythrocyte binding-like proteins from Plasmodium falciparum.
abstract: The ability of the malaria parasite, Plasmodium falciparum, to proliferate within the human host depends on its invasion of erythrocytes. Erythrocyte binding-like (EBL) proteins play crucial roles in the attachment of merozoites to human erythrocytes by binding to specific receptors on the cell surface. In this study, we have carried out a bioinformatics analysis of the three EBL proteins EBA-140, EBA-175 and EBA-181 and show that they contain a large amount of intrinsic disorder in particular within the RIII-V domains. The functional role of these domains has so far not been identified, although antibodies raised against these regions were shown to inhibit parasite invasion. Here, we obtain a more complete structural and dynamic view of the EBL proteins by focusing on the biophysical characterization of a smaller construct of the RIII-V regions of EBA-181 (EBA-181945-1097). We show using a number of techniques that EBA-181945-1097 is intrinsically disordered, and we obtain a detailed structural and dynamic characterization of the protein at atomic resolution using nuclear magnetic resonance (NMR) spectroscopy. Our results show that EBA-181945-1097 is essentially a statistical coil with the presence of several turn motifs and does not possess transiently populated secondary structures as is common for many intrinsically disordered proteins that fold via specific, pre-formed molecular recognition elements.
authors.affiliation: Faculty of Natural Sciences and Institute for Science & Technology in Medicine, Keele University, Staffordshire ST5 5BG, UK; Life Sciences Group, Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France; ESRF, 71 avenue des Martyrs, CS 40220, 38043 Grenoble Cedex 9, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Blanc
authors.affiliation: Wits Research Institute for Malaria (WRIM), Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Coetzer
authors.affiliation: Univ. Grenoble Alpes, IBS, F-38044 Grenoble, France; CNRS, IBS, F-38044 Grenoble, France; CEA, DSV, IBS, F-38044 Grenoble, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
authors.affiliation: Life Sciences Group, Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Haertlein
authors.affiliation: Faculty of Natural Sciences and Institute for Science & Technology in Medicine, Keele University, Staffordshire ST5 5BG, UK; ESRF, 71 avenue des Martyrs, CS 40220, 38043 Grenoble Cedex 9, France.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Mitchell
authors.affiliation: Faculty of Natural Sciences and Institute for Science & Technology in Medicine, Keele University, Staffordshire ST5 5BG, UK; Life Sciences Group, Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France.
authors.forename: V Trevor
authors.initials: VT
authors.lastname: Forsyth
authors.affiliation: Univ. Grenoble Alpes, IBS, F-38044 Grenoble, France; CNRS, IBS, F-38044 Grenoble, France; CEA, DSV, IBS, F-38044 Grenoble, France. Electronic address: malene.ringkjobing-jensen@ibs.fr.
authors.forename: Malene Ringkjøbing
authors.initials: MR
authors.lastname: Jensen
keywords: Chemical shift; Disorder prediction; Erythrocyte binding-like protein; Malaria; Nuclear magnetic resonance; Residual dipolar coupling