Article
- The EMBO Journal (2009) 28, 745 - 754
- doi:10.1038/emboj.2009.7
Published online: 5 February 2009
Subject Category:
Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19
Christian Neufeld1,2, Fabian V Filipp1,a, Bernd Simon1, Alexander Neuhaus3, Nicole Schüller2, Christine David3, Hamed Kooshapur4,5, Tobias Madl4,5, Ralf Erdmann3, Wolfgang Schliebs3, Matthias Wilmanns2 and Michael Sattler1,4,5
- EMBL Heidelberg, Heidelberg, Germany
- EMBL Hamburg Outstation, c/o DESY, Hamburg, Germany
- Institute for Physiological Chemistry, Department of Systems Biology, Faculty of Medicine, Ruhr University of Bochum, Bochum, Germany
- Helmholtz Zentrum München, Neuherberg, Germany
- Munich Center for Integrated Protein Science and Biomolecular NMR, Department Chemie, Technische Universität München, Garching, Germany
Correspondence to:
Michael Sattler, Institute of Structural Biology, Helmholtz Zentrum Muenchen, Ingolstaedter Landstr. 1, Neuherberg, 85764, Germany. Tel.: +49 89 28913418; Fax: +49 89 28913869; E-mail: sattler@helmholtz-muenchen.de
aPresent address: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0307, USA
Received 21 May 2008; Accepted 5 January 2009
Abstract
Protein import into peroxisomes depends on a complex and dynamic network of protein–protein interactions. Pex14 is a central component of the peroxisomal import machinery and binds the soluble receptors Pex5 and Pex19, which have important function in the assembly of peroxisome matrix and membrane, respectively. We show that the N-terminal domain of Pex14, Pex14(N), adopts a three-helical fold. Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite directionality. The molecular recognition involves conserved aromatic side chains in the Pex5 WxxxF/Y motif and a newly identified F/YFxxxF sequence in Pex19. The Pex14–Pex5 complex structure reveals molecular details for a critical interaction in docking Pex5 to the peroxisomal membrane. We show that mutations of Pex14 residues located in the Pex5/Pex19 binding region disrupt Pex5 and/or Pex19 binding in vitro. The corresponding full-length Pex14 variants are impaired in peroxisomal membrane localisation in vivo, showing that the molecular interactions mediated by the N-terminal domain modulate peroxisomal targeting of Pex14.
Keywords:
- import receptor,
- NMR,
- peroxisome biogenesis,
- peroxisomes,
- structural biology
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