Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1

Abstract

E1 enzymes facilitate conjugation of ubiquitin and ubiquitin-like proteins through adenylation, thioester transfer within E1, and thioester transfer from E1 to E2 conjugating proteins. Structures of human heterodimeric Sae1/Sae2-Mg · ATP and Sae1/Sae2-SUMO-1-Mg · ATP complexes were determined at 2.2 and 2.75 Å resolution, respectively. Despite the presence of Mg · ATP, the Sae1/Sae2-SUMO-1-Mg · ATP structure reveals a substrate complex insomuch as the SUMO C-terminus remains unmodified within the adenylation site and 35 Å from the catalytic cysteine, suggesting that additional changes within the adenylation site may be required to facilitate chemistry prior to adenylation and thioester transfer. A mechanism for E2 recruitment to E1 is suggested by biochemical and genetic data, each of which supports a direct role for the E1 C-terminal ubiquitin-like domain for E2 recruitment during conjugation. © 2005 European Molecular Biology Organization.