The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein
AbstractMisfolded proteins from the endoplasmic reticulum (ER) are transported back into the cytosol for degradation via the ubiquitin-proteasome system. The human cytomegalovirus protein US11 hijacks this ER-associated protein degradation (ERAD) pathway to downregulate human leukocyte antigen (HLA) class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. Recently, we identified the E3 ubiquitin ligase transmembrane protein 129 (TMEM129) as a key player in this process, where interference with TMEM129 activity in human cells completely abrogates US11-mediated class I degradation. Here, we set out to further characterize TMEM129. We show that TMEM129 is a non-glycosylated protein containing a non-cleaved signal anchor sequence. By glycosylation scanning mutagenesis, we show that TMEM129 is a tri-spanning ER-membrane protein that adopts an Nexo–Ccyto orientation. This insertion in the ER membrane positions the C-terminal really interesting new gene (RING) domain of TMEM129 in the cytosol, making it available to catalyze ubiquitination reactions that are required for cytosolic degradation of secretory proteins. View Full-Text
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van de Weijer, M.L.; van Muijlwijk, G.H.; Visser, L.J.; Costa, A.I.; Wiertz, E.J.H.J.; Lebbink, R.J. The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein. Viruses 2016, 8, 309.
van de Weijer ML, van Muijlwijk GH, Visser LJ, Costa AI, Wiertz EJHJ, Lebbink RJ. The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein. Viruses. 2016; 8(11):309.Chicago/Turabian Style
van de Weijer, Michael L.; van Muijlwijk, Guus H.; Visser, Linda J.; Costa, Ana I.; Wiertz, Emmanuel J.H.J.; Lebbink, Robert J. 2016. "The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein." Viruses 8, no. 11: 309.
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