Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway

Abstract

Import of peroxisomal matrix proteins is essential for peroxisome biogenesis. Genetic and biochemical studies using a variety of different model systems have led to the discovery of 23 PEX genes required for this process. Although it is generally believed that, in contrast to mitochondria and chloroplasts, translocation of proteins into peroxisomes involves a receptor cycle, there are reported differences of an evolutionary conservation of this cycle either with respect to the components or the steps involved in different organisms. We show here that the early steps of protein import into peroxisomes exhibit a greater similarity than was thought previously to be the case. Pex20p of Yarrowia lipolytica, Pex18p and Pex21p of Saccharomyces cerevisiae and mammalian Pex5pL fulfil a common function in the PTS2 pathway of their respective organisms. These non-orthologous proteins possess a conserved sequence region that most likely represents a common PTS2-receptor binding site and di-aromatic pentapeptide motifs that could be involved in binding of the putative docking proteins. We propose that not necessarily the same proteins but functional modules of them are conserved in the early steps of peroxisomal protein import.

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

“…Alignment of the sequences of the Pex7p coreceptors indicated common regions at the Cterminal end of S. cerevisiae Pex18p/Pex21p and Y. lipolytica Pex20p, in N. crassa Pex20p, and in the N-terminal half of human PEX5L (Figure 2A) (Matsumura et al, 2000;Einwachter et al, 2001). Part of this conserved sequence overlaps with the sequence encoded by the additional exon that distinguishes between PEX5S and PEX5L.…”

“…The auxiliary protein(s) for Pex7p-mediated import varies depending on the species (Figure 3): Pex18p and Pex21p in S. cerevisiae (Purdue et al, 1998); Pex20p in Hansenula polymorpha (Otzen et al, 2005), Neurospora crassa (Sichting et al, 2003), Pichia pastoris (Leon et al, 2006b) and Yarrowia lipolytica (Einwachter et al, 2001); and PEX5 in plants (Hayashi et al, 2005;Woodward and Bartel, 2005) and mammals. In mammals, only the PEX5L isoform can interact with PEX7 , and it is essential for PTS2 import (Matsumura et al, 2000).…”

“…Domain mapping identified a 21-amino-acid sequence required for Pex7p interaction and full PTS2 rescue activity, which is conserved in mammalian PEX5L and S. cerevisiae Pex18p and Pex21p ). Mis-sense mutation of a universally conserved serine residue in the centre of the common sequence was shown to disrupt Pex7p binding in all species (Matsumura et al, 2000;Einwachter et al, 2001). In A. thaliana, the pex5-1 mis-sense mutant of this same serine residue is competent for PTS1 import, but deficient in PTS2 import (Woodward and Bartel, 2005).…”

“…The universal presence of this docking motif in PTS2 co-receptors has been proposed to result from evolutionary conservation of the functional module, rather than the entire protein (Einwachter et al, 2001).…”

Hansenula polymorphaAat2p is targeted to peroxisomes via a novel Pex20p‐dependent pathway

“…The cognate receptor for this motif is Pex7p. However, unlike the PTS1 pathway, PTS2 import requires the Pex20p family of coreceptor proteins in yeast and fungi 13, 14 or a long isoform of Pex5p in higher eukaryotes 15. Pex7p functions in cargo binding, whereas the coreceptors are required for membrane docking and recycling.…”