1. Introduction
Plasmodium falciparum  is a unicellular eukaryotic protozoan parasite that causes malaria, a catastrophic disease in many developing countries. Malaria alone is responsible for millions of deaths annually across the globe. Drug resistance in malaria parasites is a serious issue hence emphasizing discovering new drug targets and inventing novel small molecules which can target multiple pathways together ensuring reduced chances of resistance is one of the main challenges in the current malaria research effort. To explore new anti-malaria drug targets, parasite ribosome can be a new focus of research interest.
The Ribosome is a protein-synthesizing nanomachine present in all living cells. In prokaryotes, ribosome comprises of 30S small subunit and 50S larger subunit whereas in eukaryotic cells 40S and 60S are the smaller and larger subunit respectively. The building blocks of a ribosome particle are mainly rRNA and proteins. These protein molecules are exclusively associated with the ribosome and primarily engaged in their ribosomal activities but many ribosomal proteins have been discovered to perform non-ribosomal functions at a distance in a different compartment of a cell (Volarevic et al., 2000; Wan et al., 2007; Wool IG., 1996; Jiménez-Díaz et al., 2013; Tchórzewski et al., 2003). In the 60S ribosomal subunit, a structural protuberance known as stalk, which is directly involved in the interaction of the elongation factors with the ribosome during mRNA translation. The stalk is a complex of five phosphorylated proteins (P-proteins), four small acidic proteins, and a larger protein that directly interacts with the rRNA at the GTPase center during protein synthesis (Remacha et al., 1995a). In eukaryotes, there are three types of P proteins, P0, P1, and P2, wherein Saccharomyces cerevisiae  acidic P1⍺ and P1 β interact with P2β and P2⍺ respectively to form [(P1⍺-P2β)-P0-(P1β-P2⍺)] pentameric stalk (Remote et al., 1995b). In-plant, an additional P protein, P3, has been discovered to be a part of plant ribosomal stalk (Kang et al., 2016). The stoichiometry of P1 and P2 differ in different organisms and found to be in a constant exchange between ribosome and cell cytoplasm (Zinker et al., 1976). In yeast and also in human cell lines, depletion of P2 leads to an instantaneous degradation of P1(Nusspaumer et al., 2000; Martinez-Azorin et al., 2008). In Saccharomyces cerevisiae,  P0 null strain is lethal whereas P1/P2 or P1-P2 null strains do survive but growth rate diminishes significantly indicating their essential nature in cell survival (Remacha et al., 1992; Santos et al., 1995; Rodríguez-Mateos et al., 2009). These uncanny properties of ribosomal P-proteins have sparked the enthusiasm to investigate whether P-proteins in eukaryotic apicomplexan human parasites (e.g; malaria) have any extra-ribosomal indispensable functions which can be targeted for better therapeutic interventions. In the malaria-endemic area, serum of malaria immune person has been detected with antibodies against anti-P. falciparum P0 protein quite extensively and exclusively (Lobo et al., 1994; Chatterjee et al., 2000; Singh et al., 2002). To explore the possibility of a novel anti-malaria intervention using P-proteins, in a differential immunoscreen, Plasmodium falciparum  60S stalk ribosomal protein P0 (PfP0) was identified as a protective protein and subsequently localized on merozoite surface possibly involved during red blood cell invasion as understood using growth inhibition assay (GIA) (Lobo et al., 1994). In P. falciparum  ribosome, P0 interact with P1 and P2 to form the pentameric stalk [(P1–P2)-P0-(P1–P2)] (Hanson et al., 2004; Gonzalo et al., 2003; Santos et al., 1994; Francisco-Velilla et al., 2010) required in the GTPase elongation center (Uchiumi et al., 1992; Diaconu et al., 2005). While exploring eccentric properties of P0 protein in Plasmodium , a very puzzling phenotype of acidic ribosomal protein P2 was discovered (Das et al., 2012a). Ribosomal P2 protein of Plasmodium falciparum  translocates to the infected RBC (iRBC) surface as an SDS resistant oligomer and appears to play a pleiotropic role at the late trophozoite/early schizogonic stage in iRBCs (Das et al., 2012a; Das et al., 2012b). In this mini-review, we summarize recent discoveries of Plasmodium P2 protein and highlight key insights and questions which need to be pondered to understand eccentric P2 biology in malaria parasites.