EGF domain II of protein Pb28 from Plasmodium berghei interacts with monoclonal transmission blocking antibody 13.1.
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.
Sharma
Babita
B
School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India, babita2005@gmail.com
Jaiswal
Manoj Kumar
MK
Saxena
Ajay K
AK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000635:transmission; D008958:Models, Molecular; D010962:Plasmodium berghei / Q000737:chemistry* / Q000276:immunology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D012984:Software
D000911:Antibodies, Monoclonal; D015800:Protozoan Proteins