Crystal structure of a complex between the human heterodimeric SUMO E1 activating enzyme (Sae1/Sae2), SUMO-1, and Mg-ATP. SUMO (yellow) is a member of the ubiquitin and ubiquitin-like protein family and is activated by a dedicated E1 enzyme (blue, pink, and red) in an ATP-dependent process. The SUMO E1 then recruits its cognate SUMO E2 via the Ubl domain (red) to facilitate SUMO transfer between E1 and E2. Once transferred to E2, SUMO can be conjugated to protein targets directly, or through complexes mediated by E3 ligases. For further details, please see the article by Lois & Lima on pages 439-451 of this issue of The EMBO Journal.