A Proteome-Wide Perspective on Peroxisome Targeting Signal 1(PTS1)-Pex5p Affinities

摘要

Abstract: Most proteins are targeted to the peroxisomal matrix by virtue of a peroxisomal targeting signal-1n(PTS1), a short carboxy-terminal sequence specifically recognized by the PTS1 receptor Pex5p. We hadnpreviously developed a model that allowed the estimation of the affinities of many PTS1 sequences withinnthe human proteome for Pex5p that revealed a wide range of predicted affinities. We have nownexperimentally determined the affinities of the PTS1-containing peptides from 42 proteins from the humannproteome for Pex5p and show that these range over 4 orders of magnitude. These affinities correlatenreasonably well with the predicted values and are substantially more precise. In an attempt to provide anpossible explanation for the wide range of PTS1 Pex5p affinities, we compared these affinities with mRNAnlevels (as a proxy for rates of protein production) of the genes encoding these proteins in 79 human tissuesnand cell types. We note that high affinity PTS1 Pex5p interactions tend to correspond to proteins encodednby genes expressed at relatively low levels, whereas lower affinity PTS1 Pex5p interactions tend toncorrespond to proteins encoded by genes exhibiting higher levels and wider ranges of expression. Furthernanalysis revealed that these relationships are consistent with the notion that a relatively uniform pool ofnprotein Pex5p complexes is maintained for appropriate peroxisome assembly.