Notum deacylates octanoylated ghrelin.

ABSTRACT:

Objectives

The only proteins known to be modified by O-linked lipidation are Wnts and ghrelin, and enzymatic removal of this post-translational modification inhibits ligand activity. Indeed, the Wnt-deacylase activity of Notum is the basis of its ability to act as a feedback inhibitor of Wnt signalling. Whether Notum also deacylates ghrelin has not been determined.

Methods

We used mass spectrometry to assay ghrelin deacylation by Notum and co-crystallisation to reveal enzyme-substrate interactions at the atomic level. CRISPR/Cas technology was used to tag endogenous Notum and assess its localisation in mice while liver-specific Notum knock-out mice allowed us to investigate the physiological role of Notum in modulating the level of ghrelin deacylation.

Results

Mass sp

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8010218 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature