Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network
Figure 4
Validation of the dynamic salt-bridge network that controls RING E3 interaction selectivity.
A. Perturbation of critical network components displaces E105/D113 and controls E3 binding. Mutagenesis of strictly conserved residues that mediate the bridging status of D113 in UbcH8 were mutated to challenge the MD predictions (see main text and Material and Methods section for details). B. Schematic representation of the “open” and “bridged” conformations of the intra-molecular network controlling E3 interactions. Indicated are E2-specific residues as well as the conserved network residues that mediate E3 binding.