Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes.

ABSTRACT: Polyubiquitination by E2 and E3 enzymes is crucial to cell cycle control, epigenetic regulation, and development. The hallmark of the E2 family is the ubiquitin (Ub)-conjugating (UBC) domain that forms a dynamic thioester conjugate with ubiquitin (E2~Ub). Numerous studies have focused on E2 surfaces, such as the N-terminal and crossover helices, that directly interact with an E3 or the conjugated ubiquitin to stabilize the active, "closed" state of the E2~Ub. However, it remains unclear how other E2 surfaces regulate ubiquitin transfer. Here, we demonstrate the helix-turn-helix (HTH) motif of the UBC tunes the intrinsic polyubiquitination activity through distinct functions in different E2s. Interestingly, the E2^HTH motif is repurposed in UBE2S and UBE2R2 to interact with the co

SUBMITTER: Welsh KA 

PROVIDER: S-EPMC8804933 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature