Structural insights into the nanomolar affinity of RING E3 ligase ZNRF1 for Ube2N and its functional implications.

ABSTRACT: RING (Really Interesting New Gene) domains in ubiquitin RING E3 ligases exclusively engage ubiquitin (Ub)-loaded E2s to facilitate ubiquitination of their substrates. Despite such specificity, all RINGs characterized till date bind unloaded E2s with dissociation constants (K_ds) in the micromolar to the sub-millimolar range. Here, we show that the RING domain of E3 ligase ZNRF1, an essential E3 ligase implicated in diverse cellular pathways, binds Ube2N with a K_d of ∼50 nM. This high-affinity interaction is exclusive for Ube2N as ZNRF1 interacts with Ube2D2 with a K_d of ∼1 µM, alike few other E3s. The crystal structure of ZNRF1 C-terminal domain in complex with Ube2N coupled with mutational analyses reveals th

SUBMITTER: Behera AP 

PROVIDER: S-EPMC5941314 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature