Abstract
Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.
Highlights
Recent decades have seen an increasing recognition that many proteins naturally lack a defined folded state, and that their function depends instead on conformational disorder [1,2]
In order to better understand the effects of conformational disorder on the immune response, and to contribute to the development of a malaria vaccine, we have investigated merozoite surface protein 2 (MSP2)
Cβ chemical shifts of the two Cys residues confirm the presence of the single disulfide in Merozoite surface protein 2 (MSP2) [49]
Summary
Recent decades have seen an increasing recognition that many proteins naturally lack a defined folded state, and that their function depends instead on conformational disorder [1,2]. Such proteins are termed intrinsically unstructured or disordered proteins, and are found across all PLOS ONE | DOI:10.1371/journal.pone.0119899. Dynamics and Antigenicity in the Disordered Malaria Antigen MSP2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
