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1.A.101. The Peroxisomal Pore-forming Pex11 (Pex11) Family

More than thirty Pex proteins are known to participate in the biogenesis of peroxisomes, oxidative organelles involved in lipid and ROS metabolism. Pex11 homologues are constituents of the Pexoxisomal Protein Importer (PPI) Family (TC# 3.A.20). They play roles, direct or indirect, in division and proliferation of peroxisomes (Schrader et al. 1998). Mindthoff et al. 2015 showed that yeast Pex11 is a pore-forming protein, possibly sharing significant sequence similarity with TRPM cation-selective channels. The Pex11 channel is moderately cation-selective (PK+/PCl-=1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r~0.6nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da, and the channel's selectivity filter was localized. Overproduction of Pex11 resulted in acceleration of fatty acids beta-oxidation in intact cells but not in the corresponding lysates. Beta-oxidation in cells was affected by expression of the Pex11 protein carrying point mutations in the selectivity filter. These data suggested that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the beta-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of beta-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 beta-oxidation rate.  Pex11 is thus a non-selective channel responsible for transfer of metabolites across peroxisomal membrane.(Mindthoff et al. 2015).

References associated with 1.A.101 family:

Jaiteh, M., A. Taly, and J. Hénin. (2016). Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors. PLoS One 11: e0151934. 26986966
Mindthoff S., Grunau S., Steinfort LL., Girzalsky W., Hiltunen JK., Erdmann R. and Antonenkov VD. (2015). Peroxisomal Pex11 is a pore-forming protein homologous to TRPM channels. Biochim Biophys Acta. 1863(2):271-283. 26597702
Schrader, M., B.E. Reuber, J.C. Morrell, G. Jimenez-Sanchez, C. Obie, T.A. Stroh, D. Valle, T.A. Schroer, and S.J. Gould. (1998). Expression of PEX11beta mediates peroxisome proliferation in the absence of extracellular stimuli. J. Biol. Chem. 273: 29607-29614. 9792670