EGF domain II of protein Pb28 from Plasmodium berghei interacts with monoclonal transmission blocking antibody 13.1 |
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Authors: | Babita Sharma Manoj Kumar Jaiswal |
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Institution: | (1) School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India |
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Abstract: | Development of a vaccine against malaria is a major global health concern. The P28 proteins expressed on the surface of ookinetes
of Plasmodium are the targets of transmission blocking antibodies. Injection of P28 proteins in vertebrate hosts induces antibodies that
inhibit oocyst formation, blocking transmission of the parasite from mosquitos to human hosts. P28 proteins are crucial for
parasite protection inside the mosquito midgut. Despite their importance, structural details of P28 family members have not
been available to date. The purpose of this study was to structurally characterise a member of the P28 family, viz. Pb28 protein
from Plasmodium berghei, and to study the interaction of Pb28 protein with the scFv (single chain variable fragment) of TBmAb (transmission blocking
monoclonal antibody) 13.1 which blocks malaria transmission effectively. Pb28 protein and the TBmAb 13.1 scFv were modelled
separately. To decipher the antigen–antibody interaction, ZDOCK and RDOCK programs were used. Our results suggest that, as
compared to the template Pvs25, Pb28 protein has four EGF (epidermal growth factor)-like domains arranged in a triangular
form with maximum root mean square deviations (RMSDs) present in the loop regions of EGF domains II and III. With the help
of docking we were able to show that the B loop of EGF domain II of Pb28 protein interacts with the scFv of TBmAb 13.1. The
predicted probable complex of Pb28 protein and 13.1 TBmAb suggests a mechanism for transmission blocking and may help in designing
vaccine candidates in the absence of experimentally determined structures of these proteins.
An erratum to this article can be found at |
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Keywords: | Epidermal growth factor Glycosylphosphatidylinositol anchor Homology modeling P28 family Plasmodium berghei 28 protein Protein-protein docking Transmission blocking monoclonal antibody 13 1 |
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