Journal Article

The peroxisomal importomer constitutes a large and highly dynamic pore

Beck, Sabrina, Cizmowski, Christian, Krüger, Vivien, Meinecke, Michael, Wagner, Richard, Erdmann, Ralf, Schliebs, Wolfgang

2010

Overview

It remains unclear how proteins translocate across the peroxisomal membrane. Insights into a potential import pore are provided with the finding that the import receptor Pex5p forms a dynamic ion channel together with Pex14p, which can be induced to open upon receptor-cargo complex association. The peroxisomal protein import machinery differs fundamentally from known translocons (endoplasmic reticulum, mitochondria, chloroplasts, bacteria) as it allows membrane passage of folded, even oligomerized proteins 1 . However, the mechanistic principles of protein translocation across the peroxisomal membrane remain unknown. There are various models that consider membrane invagination events, vesicle fusion or the existence of large import pores. Current data show that a proteinaceous peroxisomal importomer enables docking of the cytosolic cargo-loaded receptors, cargo translocation and receptor recycling 2 . Remarkably, the cycling import receptor Pex5p changes its topology from a soluble cytosolic form to an integral membrane-bound form. According to the transient pore hypothesis, the membrane-bound receptor is proposed to form the core component of the peroxisomal import pore 3 . Here, we demonstrate that the membrane-associated import receptor Pex5p together with its docking partner Pex14p forms a gated ion-conducting channel which can be opened to a diameter of about 9 nm by the cytosolic receptor–cargo complex. The newly identified pore shows striking dynamics, as expected for an import machinery translocating proteins of variable sizes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/80/2023/2022 / 631/80/642/2013 / Acyl-CoA Oxidase - metabolism / Biology / Biomedical and Life Sciences / Cancer Research / Carrier Proteins - genetics / Cell Biology / Cell membranes / Cell receptors / Chromatography / Developmental Biology / Electrophysiological Phenomena - physiology / Enzymes / Gene Deletion / Genetic aspects / Ion Channel Gating - physiology / Ion Channels - physiology / letter / Life Sciences / Membrane Potentials - physiology / Membrane Proteins - analysis / Membrane Proteins - physiology / Membrane Transport Proteins - analysis / Membrane Transport Proteins - physiology / Membranes / Membranes, Artificial / Models, Biological / Multiprotein Complexes - chemistry / Multiprotein Complexes - isolation & purification / Multiprotein Complexes - physiology / Peroxins / Peroxisome-Targeting Signal 1 Receptor / Peroxisomes / Peroxisomes - physiology / Physiological aspects / Pores / Porins - analysis / Porins - physiology / Protein Transport - physiology / Proteins / Receptors, Cytoplasmic and Nuclear - analysis / Receptors, Cytoplasmic and Nuclear - physiology / Recycling / Repressor Proteins - analysis / Repressor Proteins - physiology / Saccharomyces cerevisiae - chemistry / Saccharomyces cerevisiae - physiology / Saccharomyces cerevisiae Proteins - analysis / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Saccharomyces cerevisiae Proteins - physiology / Stem Cells / Topology / Translocation / Ubiquitin-Protein Ligases - analysis / Ubiquitin-Protein Ligases - physiology / Unilamellar Liposomes - chemistry / Yeast