1. Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C-mannosylation.
- Author
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Yoshimoto S, Suzuki T, Otani N, Takahashi D, Toshima K, Dohmae N, and Simizu S
- Subjects
- Humans, Glycosylation, Protein Transport, Receptors, Cytokine metabolism, Mannose metabolism, Vitelline Membrane metabolism
- Abstract
C-mannosylation is a rare type of protein glycosylation whereby a single mannose is added to the first tryptophan in the consensus sequence Trp-Xaa-Xaa-Trp/Cys (in which Xaa represents any amino acid). Its consensus sequence is mainly found in proteins containing a thrombospondin type-1 repeat (TSR1) domain and in type I cytokine receptors. In these proteins, C-mannosylation affects protein secretion, intracellular localization, and protein stability; however, the role of C-mannosylation in proteins that are not type I cytokine receptors and/or do not contain a TSR1 domain is less well explored. In this study, we focused on human vitelline membrane outer layer protein 1 homolog (VMO1). VMO1, which possesses two putative C-mannosylation sites, is a 21-kDa secreted protein that does not contain a TSR1 domain and is not a type I cytokine receptor. Mass spectrometry analyses revealed that VMO1 is C-mannosylated at Trp
105 but not at Trp44 . Although C-mannosylation does not affect the extracellular secretion of VMO1, it destabilizes the intracellular VMO1. In addition, a structural comparison between VMO1 and C-mannosylated VMO1 showed that the modification of the mannose changes the conformation of three loops in VMO1. Taken together, our results demonstrate the first example of C-mannosylation for protein destabilization of VMO1., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)- Published
- 2023
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