The KEAP1-CUL3 E3 ligase complex acts as a master regulator of the oxidative stress response and is a key therapeutic target in autoimmune and neuroinflammatory diseases. A new paper from the Bullock group reveals the structural basis for KEAP1 assembly with CUL3 and offers a new generalizable TR-FRET assay platform that defines the contributions of different domains to their binding affinity. The paper reveals unexpectedly that the investigational drug CDDO does not disrupt the KEAP1-CUL3 interaction, but instead reduces the affinity of KEAP1-CUL3 binding. The work forms part of a highly productive collaboration with the lab of Ralph Mazitschek at the Broad Institute.
Research reveals basis for KEAP1-CUL3 E3 ligase assembly and inhibition by CDDO
19 May 2023
Bullock group's recent paper uncovers structural basis for KEAP1 assembly with CUL3 and offers a new generalizable TR-FRET assay platform that defines the contributions of different domains to their binding affinity.
