Proteome-wide mapping of immune features onto Plasmodium protein three-dimensional structures

Guy, A, Irani, V, Beeson, J, Webb, B, Sali, A, Richards, J and Ramsland, P 2018, 'Proteome-wide mapping of immune features onto Plasmodium protein three-dimensional structures', Scientific Reports, vol. 8, 4355, pp. 1-16.


Document type: Journal Article
Collection: Journal Articles

Title Proteome-wide mapping of immune features onto Plasmodium protein three-dimensional structures
Author(s) Guy, A
Irani, V
Beeson, J
Webb, B
Sali, A
Richards, J
Ramsland, P
Year 2018
Journal name Scientific Reports
Volume number 8
Article Number 4355
Start page 1
End page 16
Total pages 16
Publisher Nature Publishing Group
Abstract Humoral immune responses against the malaria parasite are an important component of a protective immune response. Antibodies are often directed towards conformational epitopes, and the native structure of the antigenic region is usually critical for antibody recognition. We examined the structural features of various Plasmodium antigens that may impact on epitope location, by performing a comprehensive analysis of known and modelled structures from P. falciparum. Examining the location of known polymorphisms over all available structures, we observed a strong propensity for polymorphic residues to be exposed on the surface and to occur in particular secondary structure segments such as hydrogen-bonded turns. We also utilised established prediction algorithms for B-cell epitopes and MHC class II binding peptides, examining predicted epitopes in relation to known polymorphic sites within structured regions. Finally, we used the available structures to examine polymorphic hotspots and Tajima's D values using a spatial averaging approach. We identified a region of PfAMA1 involving both domains II and III under a high degree of balancing selection relative to the rest of the protein. In summary, we developed general methods for examining how sequence-based features relate to one another in three-dimensional space and applied these methods to key P. falciparum antigens.
Subject Structural Biology (incl. Macromolecular Modelling)
Infectious Agents
DOI - identifier 10.1038/s41598-018-22592-3
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ISSN 2045-2322
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