Substrate clustering potently regulates the activity of WW-HECT domain-containing ubiquitin ligases.

ABSTRACT: The Nedd4 family of HECT domain-containing E3 ligases ubiquitinate many transcription factors and signaling proteins, and their activity is tightly regulated. Normally, intramolecular interactions curb the catalytic activity of the HECT domain, but these can be broken by the binding of PY motifs, found on substrate molecules and adaptors, to the WW domains characteristic of this E3 ligase family. This raises the prospect of substrates automatically activating the ligases, frustrating the purpose of ligase regulation. Here we show that soluble protein substrates and adaptors such as α arrestins, even with multiple PY elements, cannot activate ligase activity efficiently. However, we found that polymerization or membrane tethering of these substrates dramatically increases the ligase activit

SUBMITTER: Mund T 

PROVIDER: S-EPMC5892558 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature