Daniel Horn-Ghetko, Linus V M Hopf, Ishita Tripathi-Giesgen, Jiale Du, Sebastian Kostrhon, D Tung Vu, Viola Beier, Barbara Steigenberger, J Rajan Prabu, Luca Stier, Elias M Bruss, Matthias Mann, Yue Xiong, Brenda A Schulman
Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly...
April 11, 2024: Nature Structural & Molecular Biology