Extended Data Fig. 6: Structural features of HUWE1N.
From: HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain
a, Relief of potential clashes during catalysis. The structure of the Rsp5 HECT domain (in red), charged with Ub (in blue) and in complex with a peptide substrate (PDB 4LCD), is superimposed on the HUWE1N HECT domain from the crystal structure in the upper panel, and CryoEM Class 2 in the lower panel. b, ARM34 as a molecular hinge. The H1, H2, H3 helices of ARM34 and the N-terminal HECT helix are shown in the leftmost panel together with an overview and cartoon presentation. The two copies present in the crystal structure of an extended HUWE1 HECT domain (PDB 5LP8) are overlaid on our structure and shown in cyan. Structural rearrangements of ARM34 helices H2 and H3 are indicated. c, The position of F2105. d, Autoubiquitination activity of full-length CeHUWE1 compared to the isolated HECT domain (residues 3793-4180) followed using Ub-DyLight800.
