Peroxisomal Targeting Signal Receptor Pex5p Interacts with Cargoes and Import Machinery Components in a Spatiotemporally Differentiated Manner: Conserved Pex5p WXXXF/Y Motifs Are Critical for Matrix Protein Import

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

“…In mammals, GST (glutathione transferase)-PEX13 pull-down assays have shown that the N-terminal 100 amino acids provide a binding domain for PEX5 (Otera et al, 2002), whereas in yeast, pull-down and two-hybrid assays have shown that the C-terminal SH3 (Src homology 3) domain provides a binding site for Pex5p (Bottger et al, 2000;Urquhart et al, 2000). A. thaliana PEX7 also bind the N-terminus of PEX13 in a yeast two-hybrid assay (Mano et al, 2006).…”

“…The N-terminus is protected from chemical or proteolytic cleavage Oliveira et al, 2002). This portion of PEX14 has been shown to interact directly with PEX5 via the W-X 3 -F/Y pentapeptide repeat units of the Nterminal half of PEX5 (Schliebs et al, 1999;Nito et al, 2002;Otera et al, 2002). Whether this interaction takes place within the membrane or on the luminal side remains to be determined.…”

“…Immunoprecipation of in vitro-imported PEX5L and PEX7 showed that PEX5 was predominantly associated with PEX14, whereas PEX7 was predominantly associated with PEX13 (Miyata et al, 2009). Although the PEX5L co-receptor is capable of independently and directly binding PEX14 and PEX13 (Otera et al, 2002), the yeast co-receptors Pex18/Pex21p require Pex7p to bind Pex14p and Pex13p (Stein et al, 2002). Pex13p can bind directly to Pex7p in S. cerevisiae (Girzalsky et al, 1999) and A. thaliana (Mano et al, 2006).…”

A Novel Pex14 Protein-interacting Site of Human Pex5 Is Critical for Matrix Protein Import into Peroxisomes

“…The number of the conserved WXXX(F/Y) motifs varies depending on the species with, for example, two in yeast or seven in human Pex5 (11). It was shown that each of the seven WXXX(F/Y) motifs of the human PTS1 receptor can interact with the highly conserved N-terminal domain (NTD) of Pex14 with equilibrium dissociation constants in the nanomolar range (12,13). A recent biophysical study showed that the presence of multiple WXXX(F/Y) motifs in the N terminus of Pex5 allows the formation of higher order complexes with the Pex14-NTD in vitro, although it is not clear whether this also reflects the situation in peroxisomes in vivo (14,15).…”

Peroxisome Function, Biogenesis, and Dynamics in Plants

“…Yeast PEX13 interacts with PEX14 via a C-terminal Src homology 3 (SH3) domain and an intraperoxisomal sequence; this interaction is essential for matrix protein import (Schell-Steven et al, 2005). PEX13 also binds PEX5 and PEX7 in yeast (Douangamath et al, 2002;Stein et al, 2002;Pires et al, 2003) and mammals (Otera et al, 2002). Although Arabidopsis PEX13 does bind to PEX7 (Mano et al, 2006), Arabidopsis PEX13 lacks a recognizable SH3 domain (Boisson-Dernier et al, 2008), and PEX5-PEX13 interactions have not been reported in plants (Mano et al, 2006).…”