Mr.Atul
Plasmodium falciparum
Title: Identification of novel P. falciparum Kelch13 interacting partners via Co-immunoprecipitation (Co-IP) and mass spectrometry
Biography
Biography: Mr.Atul
Abstract
The emergence of resistance against the frontline antimalarials- Artemisinin (ART) combination therapies (ACTs) is of great concern for South East Asia region and in light of recent reports from India, too. Phenotypically, the delayed parasite clearence represents ART resistance and the association of P. falciparum Kelch 13 (PfK13) gene mutations with ART resistance have drawn focus of researchers towards delineating the role of PfK13 in malaria life cycle and in emergence of ART resistance. The kelch motif of PfK13 protein is well conserved among all the Plasmodium spp. We have identified three novel proteins through co-immunoprecipitation of PfK13-interacting partners with anti-PfK13 antibodies and further analysis via mass spectrometry. These proteins have been previously implicated in critical life processes of malaria parasite viz. 1) thioredoxin-like mero protein (PF3D7_1104400)- reported for a crucial role in erythrocyte invasion; 2) pyridoxal kinase (PF3D7_0616000)- potential involvement in detoxification of reactive oxygen species and 3) trafficking protein particle complex subunit 3, (PF3D7_0418500)- putative role in vesicular trafficking. Homology modeling and protein-protein docking results have also identified highly conserved residues in the shallow pocket of the kelch domain of PfK13, as a hot-spot for binding with other interacting proteins. Understanding the functional importance of these protein-protein interactions (PPIs) would provide significant molecular insights in delineating the role of PfK13, in emergence of ART resistance.