Figure I.

Model of substrate ubiquitylation or polyubiquitylation by UbK63 chains by enzymes of the HECT-domain E3 family. (A) The HECT N lobe binds the charged UbcH5B-Ub (active cysteine represented by a red sphere) thioester (PDB code 3JW0) and transfers Ub (B) to the catalytic cysteine (green sphere) in the C lobe (PDB code 4BBN). (C) The C lobe-Ub thioester then rotates 130° to bring the donor Ub to the substrate-binding site, where it can be ligated to an acceptor lysine in the substrate (PDB code 4LCD).