Mapping the Cargo Protein Membrane Translocation Step into the PEX5 Cycling Pathway

• Type: Article in International Scientific Journal
• Date: 2009

Authors

alencastre, is (Author) Other; rodrigues, ta (Author) Other; grou, cp (Author) Other; fransen, m (Author) Other; sa-miranda, c (Author) Other; azevedo, je (Author) FCUP

Journal

Title: Journal of Biological Chemistry

Vol. 284 No. 8

Pages: 27243-27251

ISSN: 0021-9258

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 14 Citations

Other information

Authenticus ID: P-003-F39

DOI: 10.1074/jbc.M109.032565

Abstract (EN): Newly synthesized peroxisomal matrix proteins are targeted to the organelle by PEX5, the peroxisomal cycling receptor. Over the last few years, valuable data on the mechanism of this process have been obtained using a PEX5-centered in vitro system. The data gathered until now suggest that cytosolic PEX5. cargo protein complexes dock at the peroxisomal docking/translocation machinery, where PEX5 becomes subsequently inserted in an ATP-independent manner. This PEX5 species is then monoubiquitinated at a conserved cysteine residue, a mandatory modification for the next step of the pathway, the ATP-dependent dislocation of the ubiquitin-PEX5 conjugate back into the cytosol. Finally, the ubiquitin moiety is removed, yielding free PEX5. Despite its usefulness, there are many unsolved mechanistic aspects that cannot be addressed with this in vitro system and that call for a cargo protein-centered perspective instead. Here we describe a robust peroxisomal in vitro import system that provides this perspective. The data obtained with it suggest that translocation of a cargo protein across the peroxisomal membrane, including its release into the organelle matrix, occurs prior to PEX5 ubiquitination.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9