Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP to GLU substitution in an intra-molecular salt-bridge network.

ABSTRACT: Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an "open", binding competent, and a "closed", binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch

SUBMITTER: van Wijk SJ 

PROVIDER: S-EPMC3486841 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature