Novel organelle-targeting signals in viral proteins

INTRODUCTION Peroxisomes are vital cellular organelles controlling important metabolic functions like hydrogen peroxide degradation, fatty acid metabolism, gluconeogenesis, toxin degradation, etc. (Flatmark et al., 1988; van den Bosch et al., 1992; Masters, 1997; Lopez-Huertas et al., 2000). Certain human metabolic disorders such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease and rhizomelic chondrodysplasia punctata are associated with the peroxisomal defect in protein import and/or biogenesis (Gould and Valle, 2000). Intracellular transport of proteins into peroxisomes depends on either type 1 peroxisomal targeting signal (PTS1) or, type 2 (PTS 2). Type 1 signal sequence is a tripeptide motif present in the carboxy terminal of the protein (consensus sequence [STAGQCN]-[KRH]-[LIVMAFY]; Gould et al., 1987, 1989; Swinkels et al., 1991; Olivier et al., 2000). Whereas, PTS2 constitutes a combination of nine amino acid bipartite sequences (consensus [RKS]-[ILVH]-x(5)-[QH]-[LAE]) in the N-terminal half of the protein (Gould et al., 1989; Swinkels et al., 1991; Terlecky et al., 1996). Receptors for PTS1 and PTS2 have been identified as PEX5 and PEX7 respectively (Terlecky et al., 1996; Lametschwandtner et al., 1998; Subramani, 1998). The first report of PTS was in the firefly luciferase gene more than a decade ago (Gould et al., 1987, 1989). Following its discovery, except for viruses, virtually all eukaryotes, parasites and fungi have been identified to have PTS-containing proteins and demonstrated to target such proteins to the organelle (Fung and Clayton, 1991; Aitchison et al., 1992; Subramani, 1998). Recently we identified the presence of a functional and conserved PTS1 in one of the rotaviral proteins (VP4) which prompted us to look into other viral protein sequences available in the database for potential PTS1 and PTS2 motifs.