Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13

The ubiquitin conjugating enzyme complex Mms2-Ubc13 plays a key role in pos t-replicative DNA repair in yeast and the NF-kappaB signal transduction pat hway in humans. This complex assembles novel polyubiquitin chains onto yet uncharacterized protein targets. Here we report the crystal structure of a complex between hMms2 (Uev1) and hUbc13 at 1.85 Angstrom resolution and a s tructure of free hMms2 at 1.9 Angstrom resolution. These structures reveal that the hMms2 monomer undergoes a localized conformational change upon int eraction with hUbc13. The nature of the interface provides a physical basis for the preference of Mms2 for Ubc13 as a partner over a variety of other structurally similar ubiquitin-conjugating enzymes. ne structure of the hMm s2-hUbc13 complex provides the conceptual foundation for understanding the mechanism of Lys 63 multiubiquitin chain assembly and for its interactions with the RING finger proteins Rad5 and Traf6.