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

Nature Structural Biology volume 7, pages 1091–1095 (2000)Cite this article

A Corrigendum to this article was published on 01 October 2002

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.

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Figure 1: Binding of human PEX5 constructs with lissamine sulfonamide modified pentapeptides.
Figure 2: Schematic views of the PEX5–PTS1 complex.
Figure 3: Recognition of the PTS1 containing peptide.
Figure 4: Relationship of peptide with the TPR clusters.

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Acknowledgements

We thank D. Leahy, J. Beneken, and C. Dann for technical assistance and many helpful discussions, L. Brand, D. Toptygin, and A. Russo for the use of and assistance with the spectrofluorometer, N. Zachara for assistance with the SMART analysis, and A. Guerrerio for valuable assistance with the design of the anisotropy experiments and data analysis. This work was supported by grants from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Gregory J. Gatto Jr. & Jeremy M. Berg

  2. Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Brian V. Geisbrecht & Stephen J. Gould

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  1. Gregory J. Gatto Jr.
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  2. Brian V. Geisbrecht
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  4. Jeremy M. Berg
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Correspondence to Jeremy M. Berg.

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Gatto, G., Geisbrecht, B., Gould, S. et al. Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nat Struct Mol Biol 7, 1091–1095 (2000). https://doi.org/10.1038/81930

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