title: A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities.
abstract: Most proteins are targeted to the peroxisomal matrix by virtue of a peroxisomal targeting signal-1 (PTS1), a short carboxy-terminal sequence specifically recognized by the PTS1 receptor Pex5p. We had previously developed a model that allowed the estimation of the affinities of many PTS1 sequences within the human proteome for Pex5p that revealed a wide range of predicted affinities. We have now experimentally determined the affinities of the PTS1-containing peptides from 42 proteins from the human proteome for Pex5p and show that these range over 4 orders of magnitude. These affinities correlate reasonably well with the predicted values and are substantially more precise. In an attempt to provide a possible explanation for the wide range of PTS1-Pex5p affinities, we compared these affinities with mRNA levels (as a proxy for rates of protein production) of the genes encoding these proteins in 79 human tissues and cell types. We note that high affinity PTS1-Pex5p interactions tend to correspond to proteins encoded by genes expressed at relatively low levels, whereas lower affinity PTS1-Pex5p interactions tend to correspond to proteins encoded by genes exhibiting higher levels and wider ranges of expression. Further analysis revealed that these relationships are consistent with the notion that a relatively uniform pool of protein-Pex5p complexes is maintained for appropriate peroxisome assembly.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Debdip
authors.initials: D
authors.lastname: Ghosh
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Berg
mesh_terms: D000595:Amino Acid Sequence; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*
chemical_list: C529762:PEX5L protein, human; D010446:Peptide Fragments; D020543:Proteome; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear