Katharine M Wright, Sara Nathan, Hanjie Jiang, Wendy Xia, HyoJeon Kim, Nourdine Chakouri, Justin N Nwafor, Lucile Fossier, Lakshmi Srinivasan, Zan Chen, Tatiana Boronina, Jeremy Post, Suman Paul, Robert N Cole, Manu Ben-Johny, Philip A Cole, Sandra B Gabelli
NEDD4L is a HECT-type E3 ligase that catalyzes the addition of ubiquitin to intracellular substrates such as the cardiac voltage-gated sodium channel, NaV 1.5. The intramolecular interactions of NEDD4L regulate its enzymatic activity which is essential for proteostasis. For NaV 1.5, this process is critical as alterations in Na+ current is involved in cardiac diseases including arrhythmias and heart failure. In this study, we perform extensive biochemical and functional analyses that implicate the C2 domain and the first WW-linker (1,2-linker) in the auto-regulatory mechanism of NEDD4L...
February 1, 2024: Journal of Biological Chemistry