PXA1, a possible Saccharomyces cerevisiae ortholog of the human adrenoleukodystrophy gene.

The adrenoleukodystrophy protein (ALDp) is an ATP-binding cassette (ABC) transporter in the human peroxisome membrane. It is defective in X chromosome-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder with impaired peroxisomal oxidation of very long chain fatty acids. We report cloning and characterization of PXA1, a yeast gene encoding a protein (Pxa1p) exhibiting high similarity to ALDp. Disruption of PXA1 results in impaired growth on oleic acid and reduced ability to oxidize oleate. Pxa1p is peroxisome associated; however, in the PXA1 mutant yeast, as in ALD cells, peroxisomes are morphologically intact. Disruption of a second yeast gene, YKL741, which encodes a more distantly related ALDp homolog (Yk174p), in either wild-type or PXA1 mutant yeast, results in a growth phenotype identical to that of the PXA1 mutant. This result suggests that Yk1741p and Pxa1p may be subunits of the same transporter. Sequence analysis of Pxa1p, ALDp, and related ABC transporters reveals a possible fatty acid binding domain and a 14-amino acid EAA-like motif, previously described only in prokaryotes. Because of the similarities in sequence and function, we propose that Pxa1p is the Saccharomyces cerevisiae ortholog of ALDp.

Evolving discriminative motifs for recognizing proteins imported to the peroxisome via the PTS2 pathway

Peroxisomes are small subcellular compartments that utilize proteins manufactured in the cytoplasm. Proteins use one of two peroxisomal import pathways. This paper presents a simple evolutionary search for a motif that describes the signal used by one of the two pathways: PTS2. The evolved motif has a discriminative accuracy exceeding previously manually curated motifs and can be used to screen genomic data for putative peroxisomal proteins.