title: Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth.
abstract: Elucidating the molecular mechanisms of the host-parasite interaction during red cell invasion by Plasmodium is important for developing 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 parasite growth. Interaction of this parasite ligand with 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. Previously, we identified band 3 as the chymotrypsin-sensitive erythrocyte receptor for the P4region, but the other receptor, binding to P2region, 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 P2and not by the P4region of this parasite ligand. Interaction between P2and basigin is stabilized through multiple amino acid residues, but Gly-171 and Leu-175 of P2were more critical. These two amino acids were also critical for parasite growth. Synthetic peptides P2and P4of 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 P2and P4regions, 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.
authors.affiliation: From the Department of Biotechnology, All India Institute of Medical Sciences, New Delhi-110029 and rathoresumit@gmail.com.
authors.forename: Sumit
authors.initials: S
authors.lastname: Rathore
authors.affiliation: From the Department of Biotechnology, All India Institute of Medical Sciences, New Delhi-110029 and.
authors.forename: Sheena
authors.initials: S
authors.lastname: Dass
authors.affiliation: From the Department of Biotechnology, All India Institute of Medical Sciences, New Delhi-110029 and.
authors.forename: Divya
authors.initials: D
authors.lastname: Kandari
authors.affiliation: the International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Kaur
authors.affiliation: the International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Mayank
authors.initials: M
authors.lastname: Gupta
authors.affiliation: From the Department of Biotechnology, All India Institute of Medical Sciences, New Delhi-110029 and ydsharma@hotmail.com ydsharma_aiims@yahoo.com.
authors.forename: Yagya D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism*; D051926:Basigin / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000493:pharmacokinetics; D010966:Plasmodium vivax / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D000072417:Protein Domains
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000953:Antigens, Protozoan; C497886:BSG protein, human; D010455:Peptides; C454201:SLC4A1 protein, human; D051926:Basigin
keywords: alanine scanning; erythrocyte; malaria; membrane protein; parasite; peptides; protein-protein interaction; receptor