An additional primary proteolytic processing site in merozoite surface protein-1 of Plasmodium berghei

The merozoite surface protein-1 (MSP-1) is a relatively abundant protein which has been found in all Plasmodium species examined [1,2]. MSP-1 is synthesized as a high molecular mass ( 200 kDa) precursor protein which is proteolytically processed into smaller fragments. Proteolytic processing of MSP-1 is a two-step procedure characterized by primary and secondary processing events [3]. Primary processing occurs at, or just before, terminal merozoite differentiation and release and results in the formation of a noncovalent polypeptide complex with fragments of approximately 83, 30, 38 and 42 kDa [4]. The 42 kDa C-terminal fragment is further processed to 33 and 19 kDa fragments at the time of merozoite invasion [5]. This secondary processing is catalyzed by a Ca-activated serine protease which results in the shedding of a soluble MSP-1 complex [6]. The remaining glycosyl-phosphatidylinositol-anchored 19 kDa fragment [7] contains two epidermal growth factor-like modules [8] and is carried into the erythrocyte upon merozoite invasion [9]. Comparison of the MSP-1 sequence from P. berghei with other rodent parasite MSP-1 sequences [10–12] revealed four major interspecies variable regions, or blocks (Jennings et al., in preparation). The first (i.e., most N-terminal) of these variable blocks was cloned from a lgt11 cDNA expression library screened with two different mAbs against PbMSP-1 [13]. The mAbs, designated as mAb-F4.4 and mAb-L1.6, were generated from mice immune to P. berghei [14]. Variable block 1 (VB1) contains seven degenerate Abbre6iations: LT-B, B subunit of E. coli labile toxin; MSP1, merozoite surface protein-1; VB1, variable block 1. * Corresponding author. Tel.: +1 504 5842507; fax: +1 504 5996686; e-mail: wiser@mailhost.tcs.tulane.edu 1 Present address: Department of Biology, City College of San Francisco, San Francisco, CA 94112, USA. 2 Present address: Michigan Department of Community Health, P.O. Box 30035, Lansing, MI 48909, USA.