Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C-mannosylation.

Autor: Yoshimoto S; Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan., Suzuki T; Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Japan., Otani N; Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan., Takahashi D; Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan., Toshima K; Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan., Dohmae N; Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Japan., Simizu S; Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Jazyk: angličtina
Zdroj: FEBS open bio [FEBS Open Bio] 2023 Mar; Vol. 13 (3), pp. 490-499. Date of Electronic Publication: 2023 Jan 30.
DOI: 10.1002/2211-5463.13561
Abstrakt: 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 Trp 44 . 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.)
Databáze: MEDLINE
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