Clusters of malaria parasites growing inside human red blood cells.

Mike Blackman : The P. falciparum SERA family of papain-like proteins

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Proteolytic processing of SERA5 by SUB1

Figure 1: Proteolytic processing of SERA5 by SUB1 releases its central papain-like domain (here labelled P56). 

Upon its discharge in the parasite parasitophorous vacuole, SUB1 comes into contact with a set of vacuolar proteins that include members of a protein family called the serine-rich antigens (SERA). In P. falciparum there are 9 SERA family genes, 8 of which are encoded by a tandem array of genes on chromosome 2. The SERA proteins are unified by the presence of a central domain with sequence and structural homology to the cysteine protease papain.

In asexual blood stages only two SERA family members - SERA5 and SERA6 - appear essential, and we have shown that both of these proteins are cleaved by SUB1 to release the central papain-like domain (Yeoh et al., 2007; Ruecker et al., 2012).

One hypothesis we are pursuing is that cleavage of the SERA proteins by SUB1 activates their function. Whilst SERA6 possess a Cys residue at the position of the canonical nucleophile, and may possess protease activity (Ruecker et al., 2012), SERA5 does not play an enzymatic role in the parasite life cycle (Stallmach et al., 2015).

We want to identify the function(s) and substrates(s) of SERA5 and SSERA6 and to understand the biological significance of their processing by SUB1.