NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly.

ABSTRACT: Eukaryotic cell biology depends on cullin-RING E3 ligase (CRL)-catalysed protein ubiquitylation¹, which is tightly controlled by the modification of cullin with the ubiquitin-like protein NEDD8^2-6. However, how CRLs catalyse ubiquitylation, and the basis of NEDD8 activation, remain unknown. Here we report the cryo-electron microscopy structure of a chemically trapped complex that represents the ubiquitylation intermediate, in which the neddylated CRL1^β-TRCP promotes the transfer of ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D to its recruited substrate, phosphorylated IκBα. NEDD8 acts as a nexus that binds disparate cullin elements and the RING-activated ubiquitin-linked UBE2D. Local structural remodelling of NEDD8 and large-scale movements of C

SUBMITTER: Baek K 

PROVIDER: S-EPMC7050210 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature