A member of the Plasmodium falciparum Pf60 multigene family codes for a nuclear protein expressed by readthrough of an internal stop codon

Four large multigene families have been described in Plasmodium falciparum malaria parasites (var, rif, stevor and Pf60). var and rif genes code for e rythrocyte surface proteins and undergo clonal antigenic variation. We repo rt here the characterization of the first Pf60 gene. The 6.1 gene is consti tutively expressed by all mature blood stages and codes for a protein locat ed within the nucleus. It has a single copy, 7-exon, 5' domain, separated b y an internal stop codon from a 3' domain that presents a high homology wit h var exon II. Double-site immunoassay and P. falciparum transient transfec tion using the reporter luciferase gene demonstrated translation through th e internal ochre codon. The 6.1 N-terminal domain has no homology with any protein described to date. Sequence analysis identified a leucine zipper an d a putative nuclear localization signal and showed a high probability for coiled coils. Evidence for N-terminal coiled coil-mediated protein interact ions was obtained. This identifies the 6.1 protein as a novel nuclear prote in. These data show that the Pf60 and var genes form a superfamily with a c ommon 3' domain, possibly involved in regulating homo- or heteromeric inter actions.