Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p

• Published in: The EMBO journal Vol. 29; no. 24; pp. 4083 - 4093
• Main Authors: Sato, Yasuhiko, Shibata, Hiroyuki, Nakatsu, Toru, Nakano, Hiroaki, Kashiwayama, Yoshinori, Imanaka, Tsuneo, Kato, Hiroaki
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.12.2010; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Amino Acid Sequence; Binding Sites; Circular Dichroism; crystal structure; Crystallography, X-Ray; EMBO20; EMBO40; Lipoproteins - chemistry; Lipoproteins - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Models, Molecular; Molecular Sequence Data; Neurons; peroxin; Peroxins; peroxisomal membrane protein; Protein Binding; Protein Conformation; Protein Structure, Quaternary; protein-protein interactions; Proteins; Sequence Alignment; Translocation; peroxisomal membrane protein; protein–protein interactions; crystal structure; peroxin
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2010.293

Peroxisomes require peroxin (Pex) proteins for their biogenesis. The interaction between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which resides in the cytosol, is crucial for peroxisome formation and the post‐translational targeting of peroxisomal membrane proteins (PMPs). It is not known how Pex3p promotes the specific interaction with Pex19p for the purpose of PMP translocation. Here, we present the three‐dimensional structure of the complex between a cytosolic domain of Pex3p and the binding‐region peptide of Pex19p. The overall shape of Pex3p is a prolate spheroid with a novel fold, the ‘twisted six‐helix bundle.’ The Pex19p‐binding site is at an apex of the Pex3p spheroid. A 16‐residue region of the Pex19p peptide forms an α‐helix and makes a contact with Pex3p; this helix is disordered in the unbound state. The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis. Post‐translational targeting of peroxisomal membrane proteins involves the interaction of the cytosolic receptor and chaperone Pex19p with its docking protein Pex3p at the peroxisomal membrane. This study presents the crystal structure of the cytosolic domain of Pex3p in complex with a Pex19p peptide.