Title
Basigin interacts with Plasmodium vivax tryptophan-rich antigen PvTRAg38 as a second erythrocyte receptor to promote parasite growth
Author
Sumit Rathore, Sheena Dass, Divya Kandari, Inderjeet Kaur, Mayank Gupta, Yagya D. Sharma
Year
2016
Journal
The Journal of Biological Chemistry
Abstract
Elucidating molecular mechanisms of host-parasite interaction during red cell invasion by Plasmodium is important to develop newer antimalarial therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich antigen PvTRAg38, which is expressed by its merozoites, binds to host erythrocytes, and interferes with the parasite growth. Interaction of this parasite ligand to the host erythrocyte occurs through its two regions present at amino acid positions 167-178 (P2) and 197-208 (P4). Each region recognizes its own erythrocyte receptor. Earlier, we have identified Band 3 as the chymotrypsin sensitive erythrocyte receptor for P4 region but the other receptor, binding to P2 region, remained unknown. Here, we have identified Basigin as the second erythrocyte receptor for PvTRAg38 which is resistant to chymotrypsin. The specificity of interaction between PvTRAg38 and Basigin was confirmed by direct interaction where Basigin was specifically recognized by P2 and not by P4 region of this parasite ligand. Interaction between P2 and Basigin is stabilized through multiple amino acid residues but Gly171, and Leu175 of P2 were more critical. These two amino acids were also critical for parasite growth. Synthetic peptides P2 and P4 of PvTRAg38 interfered with the parasite growth independently but had an additive effect if combined together indicating involvement of both the receptors during red cell invasion. In conclusion, PvTRAg38 binds to two erythrocyte receptors Basigin and Band 3 through P2 and P4 regions, respectively, to facilitate parasite growth. This advancement in our knowledge on molecular mechanisms of host-parasite interaction can be exploited to develop therapeutics against P. vivax malaria.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Biochemistry