HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.

ABSTRACT: HUWE1 is a universal quality-control E3 ligase that marks diverse client proteins for proteasomal degradation. Although the giant HECT enzyme is an essential component of the ubiquitin-proteasome system closely linked with severe human diseases, its molecular mechanism is little understood. Here, we present the crystal structure of Nematocida HUWE1, revealing how a single E3 enzyme has specificity for a multitude of unrelated substrates. The protein adopts a remarkable snake-like structure, where the C-terminal HECT domain heads an extended alpha-solenoid body that coils in on itself and houses various protein-protein interaction modules. Our integrative structural analysis shows that this ring structure is highly dynamic, enabling the flexible HECT domain to reach protein targets presente

SUBMITTER: Grabarczyk DB 

PROVIDER: S-EPMC7611724 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature