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Title: Functional characterization of two missense mutations in Pex5p - C11S and N526K
Authors: Carvalho, Andreia F
Grou, Cláudia P
Pinto, Manuel P
Alencastre, Inês S
Costa-Rodrigues, João
Fransen, Marc
Sá-Miranda, Clara
Azevedo, Jorge E # ×
Issue Date: 11-Jun-2007
Publisher: Elsevier
Series Title: Biochimica et Biophysica Acta. Molecular Cell Research vol:1773 issue:7 pages:1141-1148
Abstract: Most newly synthesized peroxisomal proteins are targeted to the organelle by Pex5p, the peroxisomal cycling receptor. Pex5p interacts with these proteins in the cytosol, transports them to the peroxisomal docking/translocation machinery and promotes their translocation across the organelle membrane. Finally, Pex5p is recycled back to the cytosol in order to catalyse additional rounds of transportation. Although several properties of this protein sorting pathway have been recently uncovered, we are still far from comprehending many of its basic principles. Here, we describe the mechanistic implications of two single-amino acid substitutions in Pex5p. The first mutation characterized, Cys11Ser, blocks the recycling of Pex5p back into the cytosol at the step in which stage 2 Pex5p is converted into stage 3 Pex5p. The mutation Asn526Lys, previously described in a child with neonatal adrenoleukodystrophy and shown to abolish the PTS1-binding capacity of Pex5p, results in a Pex5p protein exhibiting import capacity. Protease assays suggest that the Asn526Lys mutation causes conformational alterations at the N-terminal half of Pex5p mimicking the ones induced by binding of a PTS1-containing peptide to the normal peroxin. The implications of these findings on the mechanism of protein translocation across the peroxisomal membrane are discussed.
URI: 
ISSN: 0167-4889
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmacology Section (-)
Laboratory of Lipid Biochemistry and Protein Interactions
× corresponding author
# (joint) last author

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