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.