High impact information on PEX14

• Pex14p, an S. cerevisiae peroxin, is attached to the outer face of the peroxisomal membrane and is a component of the protein import machinery [1].
• Pex14p, a peroxisomal membrane protein binding both receptors of the two PTS-dependent import pathways [1].
• While the function of most small signaling domains is confined to binary ligand interactions, the peroxisomal Pex13p SH3 domain has the unique capacity of binding to two different ligands, Pex5p and Pex14p [2].
• Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2-dependent protein import into peroxisomes [3].
• From these and other studies we conclude that Pex17p, in addition to Pex13p and Pex14p, is the third identified component of the peroxisomal translocation machinery [4].

Biological context of PEX14

• Using the rice PEX14 cDNA as a bait in a yeast two-hybrid assay, two splice variants of the type I peroxisomal targeting signal (PTS1) receptor, OsPex5pL and OsPex5pS, were cloned from a pathogen-treated rice leaf cDNA library [5].
• In a first step of a structure-function analysis of Saccharomyces cerevisiae Pex14p, we mapped its binding sites with both receptors [6].
• In the yeast Saccharomyces cerevisiae, both Pex5p and Pex14p are able to bind Pex13p via its SH3 domain [7].

Anatomical context of PEX14

• Peroxisome formation from the preperoxisomal compartment depends on the activity of the genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix and membrane proteins, respectively [8].
• Pex14p was characterized as an integral membrane protein of peroxisomes, exposing its N- and C-terminal parts to the cytosol [9].

Associations of PEX14 with chemical compounds

• Site-directed mutagenesis of the conserved tryptophan residue within a reverse WXXXF motif abolished two-hybrid binding with the N-terminal half of Pex14p [10].
• In cells of a pex19 disruption strain (Hppex19), induced on methanol, peroxisome structures were not detectable; peroxisomal matrix proteins accumulated in the cytosol, whereas peroxisomal membrane proteins (PMPs) were mislocalized to the cytosol (Pex3p) and mitochondria (Pex14p) or strongly reduced to undetectable levels (Pex10p) [11].
• These organelles, which contained typical peroxisomal matrix and membrane proteins (alcohol oxidase, catalase, Pex3p, Pex10p and Pex14p), showed a relatively low density (1.18 g cm-3) after sucrose gradient centrifugation of WT::PAOX.PEX3(7x) homogenates, compared to normal peroxisomes (1.23 g cm-3) [12].

Physical interactions of PEX14

• On the basis of these and other published data, we propose that the C terminus of Pex14p contains the actual docking site and discuss the possibility that the N terminus could be involved in a Pex5p-Pex14p association inside the peroxisomal membrane [6].

Other interactions of PEX14

• Yeast Pex14p possesses two functionally distinct Pex5p and one Pex7p binding sites [6].
• Taken together, this indicates that in the absence of Pex13-SH3 interaction, other protein(s) is able to bind Pex5p at the peroxisome; Pex14p is a likely candidate for this function [7].
• This conclusion is supported by immunoprecipitation experiments showing that Pex14p and Pex17p coprecipitate with both PTS receptors in the absence of Pex13p [4].

References