SUMMARY PARAGRAPH for PEX5
The biogenesis of peroxisomes requires a group of protein factors referred to as peroxins which are encoded by the PEX genes. Peroxisomal proteins are synthesized on free polyribosomes and imported posttranslationally. The transport of peroxisomal matrix proteins from the cytoplasm to the peroxisome is mediated by two peroxisome-targeting signal sequences (PTS1 and PTS2). Peroxisomal membrane proteins (PMPs) are imported independently of the matrix proteins by a distinct mechanism mediated by the membrane PTS signal (mPTS) (6, 7, 8, 9 and references therein).
Pex5p mediates the import of peroxisomal matrix proteins during peroxisome biogenesis by binding to the peroxisomal targeting sequence PTS1 (8, 10). PTS1 is a carboxy-terminal tripeptide motif with the canonical sequence serine-lysine-leucine, but the first and second positions can be degenerate (3, 11 and references therein). Pex5p binds PTS1-containing proteins in the cytoplasm and delivers them to the peroxisomal membrane where the Pex5p-peroxisomal matrix protein complex interacts with the peroxisomal import machinery (12).
Two subcomplexes of the peroxisomal import machinery have been defined: the docking subcomplex comprises Pex14p, Pex17p, and Pex13p, while the translocation subcomplex contains Pex2p, Pex10p, and Pex12p. The proteins of the translocation complex expose their RING finger domains to the outer face of the peroxisomal membrane, and act downstream of Pex14p, Pex17p, and Pex13p during the peroxisomal protein import process (13). Association of both subcomplexes into a larger import complex requires Pex8p, an intraperoxisomal protein. Pex8p organizes the formation of the larger import complex from the trans side of the peroxisomal membrane and thus might enable functional communication between both sides of the membrane (13).
Although Pex5p interacts with many of the subunits in the docking and translocation complex, Pex5p may first interact with Pex14p (14). The ubiquitination of Pex5p at the peroxisomal membrane may be required for its release and recycling (15, 16, 17, 18).
Pex5p has been proposed to have multiple roles in the import of peroxisomal matrix proteins. In addition to its role as the PTS1 receptor protein, Pex5p may be involved in the import of peroxisomal matrix proteins that do not contain a PTS1 signal (5, 19). Also, Pex5p has been proposed to stabilize the formation of the docking complex (20).
Growth on oleic acid induces the expression of many peroxisomal genes. Their expression is mediated by the transcription factor complex Pip2p-Oaf1p, which binds the oleate response element (ORE) found in the promoter region of a number of these genes (21). However, although the Pip2p-Oaf1p bind the PEX5 ORE, its expression was not induced in the presence of oleic acid (22)
The carboxy-terminal region of Pex5p contains highly conserved seven tetratricopeptide repeats that are required to bind PTS1 (3, 23). The amino-terminal region contains a conserved WxxxF/Y motif that is important to bind Pex13p (24). Pex5p is conserved in fungi, plants, worms, and humans (25, 26, 27, 28). The human PEX5 encodes two isoforms, PEX5S and PEX5L. PEX5L appears to be involved in PTS2 protein import, which, in S. cerevisiae, is mediated by Pex7p, Pex18p, and Pex21p (25, 29 and references therein). Mutations in human PEX5, also known as PTS1R or PXR1, have been associated with the peroxisome biogenesis disorders neonatal adrenoleukodystrophy and Zellweger syndrome (30, 28).
Last updated: 2007-06-28