Covalent ligation of multiubiquitin chains targets eukaryotic proteins for
degradation. In such multiubiquitin chains, successive ubiquitins are linked by
an isopeptide bond involving the side chain of Lys48 and the carboxyl group of
Gly76. The crystal structure of a diubiquitin conjugate has been determined and
refined at 2.3-A resolution. The molecule has internal approximate 2-fold
symmetry with multiple hydrophobic and hydrophilic contacts along the 2-fold
axis. The structure of the diubiquitin conjugate suggests determinants for
recognition of multiubiquitin chains. A model for the interaction of diubiquitin
and a ubiquitin conjugating enzyme (E2) is proposed.