Tânia Francisco, Ana G Pedrosa, Tony A Rodrigues, Tarad Abalkhail, Hongli Li, Maria J Ferreira, Gerbrand J van der Heden van Noort, Marc Fransen, Ewald H Hettema, Jorge E Azevedo
PEX5, the peroxisomal protein shuttling receptor, binds newly synthesized proteins in the cytosol and transports them to the organelle. During its stay at the peroxisomal protein translocon, PEX5 is monoubiquitinated at its cysteine 11 residue, a mandatory modification for its subsequent ATP-dependent extraction back into the cytosol. The reason why a cysteine and not a lysine residue is the ubiquitin acceptor is unknown. Using an established rat liver-based cell-free in vitro system, we found that, in contrast to wild-type PEX5, a PEX5 protein possessing a lysine at position 11 is polyubiquitinated at the peroxisomal membrane, a modification that negatively interferes with the extraction process...
March 12, 2024: PLoS Biology