Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif

Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. By combining biochemical methods and structural biology, we show that the C-terminal SH3 domain of PEX13 mediates intramolecular interactions with a proximal FxxxF motif. The SH3 domain also binds WxxxF peptide motifs in the impor...

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Published in:Nature communications 2024-04, Vol.15 (1), p.3317-3317, Article 3317
Main Authors: Gaussmann, Stefan, Peschel, Rebecca, Ott, Julia, Zak, Krzysztof M., Sastre, Judit, Delhommel, Florent, Popowicz, Grzegorz M., Boekhoven, Job, Schliebs, Wolfgang, Erdmann, Ralf, Sattler, Michael
Format: Article
Language:English
Subjects:
101/6
14/19
631/45/612
631/535/1266
631/535/878/1263
631/80/2023/2022
631/80/642/2013
82/80
82/83
96/63
Binding
Crystal structure
Evolutionary conservation
Humanities and Social Sciences
Imports
multidisciplinary
NMR
Nuclear magnetic resonance
Peptides
Peroxisomes
Proteins
Science
Science (multidisciplinary)
Yeast
Yeasts
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Summary:Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. By combining biochemical methods and structural biology, we show that the C-terminal SH3 domain of PEX13 mediates intramolecular interactions with a proximal FxxxF motif. The SH3 domain also binds WxxxF peptide motifs in the import receptor PEX5, demonstrating evolutionary conservation of such interactions from yeast to human. Strikingly, intramolecular interaction of the PEX13 FxxxF motif regulates binding of PEX5 WxxxF/Y motifs to the PEX13 SH3 domain. Crystal structures reveal how FxxxF and WxxxF/Y motifs are recognized by a non-canonical surface on the SH3 domain. The PEX13 FxxxF motif also mediates binding to PEX14. Surprisingly, the potential PxxP binding surface of the SH3 domain does not recognize PEX14 PxxP motifs, distinct from its yeast ortholog. Our data show that the dynamic network of PEX13 interactions with PEX5 and PEX14, mediated by diaromatic peptide motifs, modulates peroxisomal matrix import. Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. Here the authors obtain crystal structures and NMR data to show the recognition of diaromatic peptide motifs on a noncanonical surface of the PEX13 SH3 domain, revealing a dynamic network which modulates peroxisomal matrix import.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-47605-w