Gaussmann, S. ; Peschel, R.* ; Ott, J.* ; Zak, K.M. ; Sastre, J.* ; Delhommel, F. ; Popowicz, G.M. ; Boekhoven, J.* ; Schliebs, W.* ; Erdmann, R.* ; Sattler, M.
Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif.
Nat. Commun. 15:3317 (2024)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Membrane-protein Pex13p; Receptor Pex5p Interacts; Saccharomyces-cerevisiae; Evolutionary Conservation; Structural Basis; Biogenesis; Site; Translocation; Recognition; Machinery
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 15,
Heft: 1,
Seiten: ,
Artikelnummer: 3317
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-503000-001
Förderungen
EMBO Long-term Fellowship
German Federal Ministry of Research and Education (BMBF) program "Targetvalidierung fur die pharmazeutische Wirkstoffentwicklung"
BMBF VIP+
Deutsche Forschungsgemeinschaft
Copyright
Erfassungsdatum
2024-06-05