ZNRF3 and RNF43 are active monomeric E3 ligases that self-associate

ABSTRACT: Crosslinking mass spectrometry was used to identify the site of dimerization in the RING domain of ZNRF3. The two proteins, ZNRF3 and RNF43 have a key role in regulating the number of Frizzled (FZD) receptor on cells and their inactivation causes cancer. This is because they are RING E3 ligases that promote the ubiquitylation and internalisation of FZD, thereby turning off WNT signalling. Here we identify the key determinants of ubiquitin transfer by ZNRF3 and RNF43 and report the structure of the RING domain from ZNRF3. Our data indicate that the RING domain is monomeric, and that RING dimerization is not required for its ubiquitin ligase activity. However, the ectodomain of ZNRF3 forms dimers and our data supports a model where the cytoplasmic domains self-associate in cells even though RING dimerization is not required for activity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Torsten Kleffmann  

LAB HEAD: Professor Catherine Day

PROVIDER: PXD070424 | Pride | 2026-07-30

REPOSITORIES: Pride