Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168.

ABSTRACT: The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168 by ubiquitylated targets involves two distinct regions, Ub-dependent DSB recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the complex between UDM1 and Lys63-linked diUb (K63-Ub₂) and that between the C-terminally truncated UDM2 (UDM2ΔC) and K63-Ub₂. In both structures, UDM1 and UDM2ΔC fold as a single α-helix. Their simultaneous bindings to the distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains. Structural and biochemical analyses of UDM1 elucidate an Ub-binding mechanism between UDM1 and polyubiquitylated targets. Mutations of Ub-interacting residues in

SUBMITTER: Takahashi TS 

PROVIDER: S-EPMC5766498 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature