Plasmodial serine repeat antigen homologues with properties of schizont cysteine proteases

Abstract

Proteases appear to be required for critical events in the erythrocytic life cycle of malaria parasites, including the rupture of erythrocytes by mature schizonts and the subsequent invasion of erythrocytes by daughter merozoites [1,2]. This conclusion is supported by studies showing that parasite rupture and invasion of erythrocytes are inhibited by serine and cysteine protease inhibitors [1] and that the proteolytic processing of late schizont-stage proteins is required for the completion of the erythrocytic cycle [3,4]. A number of schizont protease activities have been identified biochemically [2], but limitations on available quantities of protein have made it difficult to definitively characterize these proteases or to ascertain their specific biological roles.The Plasmodium falciparum serine repeat antigen (known as SERA, SERA-1, SERP or P126 [5][6][7]) is being studied as a potential vaccine component [8]. A number of SERA homologues have been described, namely serine repeat protein homologue (SERPH [9] or SERA-2 [10]) and SERA-3 [10] from P. falciparum and five homologues from Plasmodium 6i6ax [11]. SERA and SERPH have been localized to the parasitophorous vacuole of mature schizonts [9,12], and SERA fragments are released into the bloodstream near the time of erythrocyte rupture [12]. SERA and its homologues all contain a 30 kDa 'protease domain' that has similarity in sequence to papain-family cysteine proteases, particularly near highly conserved active site residues [13] (Fig. 1A). Taken together, available data suggest that SERA and SERPH may act as late schizontAbbre6iations: SERA, serine repeat antigen; SERPH, serine repeat antigen homologue.

Apoptosis-like death as a feature of malaria infection in mosquitoes

“…All SERA proteins contain a central domain with strong homology to papain-family cysteine proteases but several SERAs, including the abundant SERA5, have a serine residue in place of the active site cysteine (Kiefer et al 1996 ;Gor et al 1998 ;Hodder et al 2003) which will undoubtedly influence the substrate specificity and inhibitor sensitivity. For example, SERA5 possesses a chymotrypsin-like protease activity, with a P1 specificity for an aromatic amino acid, which can be inhibited by a serine protease inhibitor (Hodder et al 2003).…”