RRC ID 73814
Author Yoshimoto S, Suzuki T, Otani N, Takahashi D, Toshima K, Dohmae N, Simizu S.
Title Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C-mannosylation.
Journal FEBS Open Bio
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 Trp105 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.
Published 2023-1-20
DOI 10.1002/2211-5463.13561
PMID 36680395
PMC PMC9989928
MeSH Glycosylation Humans Mannose* / metabolism Protein Transport Receptors, Cytokine / metabolism Vitelline Membrane* / metabolism
IF 2.231
Human and Animal Cells 293T(RCB2202)
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) VMO1-GH (RDB20014) VMO1-MH (RDB20015) VMO1/W105F-MH (RDB20016)