(G2)BRinging an E2 to E3

Abstract

In a recent issue of Molecular Cell, Das et al. (2009) show that the G2BR domain of gp78, a RING-family E3 ubiquitin ligase, binds the E2 Ube2g2 and induces conformational changes within Ube2g2 to allosterically enhance its interaction with cognate E3 RING domains.

Figure 1. Schematic view of allosteric regulation of the E2 Ube2g2 upon binding the G2BR from the RING E3 gp78

Ubiquitin (Ub) is represented in yellow, and the gp78 G2BR and RING domains are in green. The core domain of Ube2g2 is shown in slate, with different conformations of the β4α2 and α2α3 loops in cyan (free Ube2g2) and red (Ube2g2-G2BR). G2BR binds the Ube2g2 “backside”, opposite from the catalytic Cys89 and distal from the RING binding surface, to allosterically cause the two loops to move (black arrows). Presumably via the conformational changes, G2BR-binding reduces E1-mediated formation of a Ube2g2∼Ub thiolester complex, and increases binding to partner RING domains.