The peroxisomal importomer constitutes a large and highly dynamic pore.
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. 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. 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. 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.
Biophysik, FB Biologie/Chemie, Universität Osnabrück, Germany.
Michael
M
Meinecke
Christian
C
Cizmowski
Wolfgang
W
Schliebs
Vivien
V
Krüger
Sabrina
S
Beck
Richard
R
Wagner
Ralf
R
Erdmann
D042962:Acyl-CoA Oxidase / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D055724:Electrophysiological Phenomena / Q000502:physiology; D017353:Gene Deletion; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology; D026901:Membrane Transport Proteins / Q000032:analysis / Q000502:physiology*; D008567:Membranes, Artificial; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D000074401:Peroxins; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000502:physiology*; D018272:Porins / Q000032:analysis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000502:physiology; D012097:Repressor Proteins / Q000032:analysis / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000502:physiology; D053835:Unilamellar Liposomes / Q000737:chemistry
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008567:Membranes, Artificial; D046912:Multiprotein Complexes; C492057:PEX10 protein, S cerevisiae; C491335:PEX12 protein, S cerevisiae; C491105:PEX13 protein, S cerevisiae; C499195:PEX14 protein, S cerevisiae; C491361:PEX17 protein, S cerevisiae; C116845:PEX18 protein, S cerevisiae; C116846:PEX21 protein, S cerevisiae; C499509:PEX5 protein, S cerevisiae; D000074401:Peroxins; D000074435:Peroxisome-Targeting Signal 1 Receptor; C404515:Pex8 protein, S cerevisiae; D018272:Porins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D053835:Unilamellar Liposomes; D042962:Acyl-CoA Oxidase; C467991:POX1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases