Peroxisomal Pex11 is a pore-forming protein homologous to TRPM channels
| Autor: | Wolfgang Girzalsky, J. Kalervo Hiltunen, Sabrina Mindthoff, Vasily D. Antonenkov, Laura L. Steinfort, Silke Grunau, Ralf Erdmann |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Blotting Western Molecular Sequence Data Porins TRPM Cation Channels Saccharomyces cerevisiae Biology Pore forming protein Mass Spectrometry Peroxins 03 medical and health sciences 0302 clinical medicine TRPM Peroxisomes Protein phosphorylation Amino Acid Sequence Phosphorylation Peroxisomal targeting signal Molecular Biology Sequence Homology Amino Acid Circular Dichroism Fatty Acids Membrane Proteins Cell Biology Peroxisome Transmembrane protein Cell biology 030104 developmental biology Membrane protein Biochemistry Mutation Oxidation-Reduction 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1863(2):271-283 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2015.11.013 |
| Popis: | More than 30 proteins (Pex proteins) are known to participate in the biogenesis of peroxisomes-ubiquitous oxidative organelles involved in lipid and ROS metabolism. The Pex11 family of homologous proteins is responsible for division and proliferation of peroxisomes. We show that yeast Pex11 is a pore-forming protein sharing sequence similarity with TRPM cation-selective channels. The Pex11 channel with a conductance of Λ=4.1 nS in 1.0M KCl is moderately cation-selective (PK(+)/PCl(-)=1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r~0.6 nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da. We localized the channel's selectivity determining sequence. Overexpression of Pex11 resulted in acceleration of fatty acids β-oxidation in intact cells but not in the corresponding lysates. The β-oxidation was affected in cells by expression of the Pex11 protein carrying point mutations in the selectivity determining sequence. These data suggest that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the β-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of β-oxidation in yeast strains expressing Pex11 with mutations mimicking constitutively phosphorylated (S165D, S167D) or unphosphorylated (S165A, S167A) protein. The results suggest that phosphorylation of Pex11 is a mechanism that can control the peroxisomal β-oxidation rate. Our results disclose an unexpected function of Pex11 as a non-selective channel responsible for transfer of metabolites across peroxisomal membrane. The data indicate that peroxins may be involved in peroxisomal metabolic processes in addition to their role in peroxisome biogenesis. |
| Databáze: | OpenAIRE |
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