Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5

Jr Gatto G.J., B. V. Geisbrecht, Stephen J Gould, J. M. Berg

Research output: Contribution to journalArticle

Abstract

Many proteins contain targeting signals within their sequences that specify their delivery to particular organelles. The peroxisomal targeting signal-1 (PTS1) is a C-terminal tripeptide that is sufficient to direct proteins into peroxisomes. The PTS1 sequence closely approximates Ser-Lys-Leu-COO-. PEX5, the receptor for PTS1, interacts with the signal via a series of tetratricopeptide repeats (TPRs) within its C-terminal half. Here we report the crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence. Two clusters of three TPRs almost completely surround the peptide, while a hinge region, previously identified as TPR4, forms a distinct structure that enables the two sets of TPRs to form a single binding site. This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction.

Original languageEnglish (US)
Pages (from-to)1091-1095
Number of pages5
JournalNature Structural Biology
Volume7
Issue number12
DOIs
StatePublished - 2000

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Protein Sorting Signals
seryl-lysyl-leucine
Peptides
Peroxisomes
Protein Transport
Hinges
Molecular Structure
Organelles
Proteins
Crystal structure
Binding Sites
carboxyl radical

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. / Gatto G.J., Jr; Geisbrecht, B. V.; Gould, Stephen J; Berg, J. M.

In: Nature Structural Biology, Vol. 7, No. 12, 2000, p. 1091-1095.

Research output: Contribution to journalArticle

Gatto G.J., Jr ; Geisbrecht, B. V. ; Gould, Stephen J ; Berg, J. M. / Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. In: Nature Structural Biology. 2000 ; Vol. 7, No. 12. pp. 1091-1095.
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