HECT and RING ligases act by different mechanisms. HECT E3 ligases (top) directly catalyze the attachment of ubiquitin to the substrate, whereas in the case of RING ligases (bottom) the ubiquitin is transferred from the E2 which, with the substrate, is bound to the E3. Exactly how the catalytic action of E2 is facilitated by the RING E3 is not known. Reactive thioester bonds are shown in red; the isopeptide bond with the target (substrate) protein is shown in black.
Dikic and Robertson BMC Biology 2012 10:22 doi:10.1186/1741-7007-10-22