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PMID:20178365

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Citation

Ghosh, D and Berg, JM (2010) A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities. J. Am. Chem. Soc. 132:3973-9

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.

Links

PubMed Online version:10.1021/ja9109049

Keywords

Amino Acid Sequence; Gene Expression Regulation; Humans; Models, Molecular; Molecular Sequence Data; Peptide Fragments/chemistry; Peptide Fragments/metabolism; Peroxisomes/genetics; Peroxisomes/metabolism; Protein Binding; Protein Structure, Tertiary; Proteome/genetics; Proteome/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Receptors, Cytoplasmic and Nuclear/chemistry; Receptors, Cytoplasmic and Nuclear/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IDE

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete

HUMAN:CATA

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete

HUMAN:DCMC

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete

HUMAN:ACOT8

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete

HUMAN:IDHC

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete

HUMAN:NOS2

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50542

F

Seeded From UniProt

complete


See also

References

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