9DRJ

Cryo-EM structure of a SUMO E1-E2-SUMO1 complex.

Summary for 9DRJ

• Entry DOI: 10.2210/pdb9drj/pdb
• EMDB information: 47127
• Descriptor: SUMO-activating enzyme subunit 1, SUMO-activating enzyme subunit 2, SUMO-conjugating enzyme UBC9, ... (6 entities in total)
• Functional Keywords: sumo1, sae1, ubc9, uba2, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 133650.30

Authors

Jia, L.,Nayak, D.,Ruben, E.A.,Nayak, A.,Wasmuth, E.V.,Olsen, S.K. (deposition date: 2024-09-25, release date: 2025-10-01, Last modification date: 2025-12-24)

Primary citation

Nayak, A.,Nayak, D.,Jia, L.,Ruben, E.A.,Viswanadhapalli, S.,Dos Santos Bury, P.,Nassar, K.M.,Yu, C.H.,Tumanova, A.A.,Stratton, C.M.,Ebadi, P.,Ivanov, D.N.,Sung, P.,Vadlamudi, R.K.,Wasmuth, E.V.,Olsen, S.K.
Cryo-EM structures reveal the molecular mechanism of SUMO E1-E2 thioester transfer.
Nat.Struct.Mol.Biol., 32:2441-2453, 2025

PubMed Abstract: Post-translational modification of proteins by SUMO (small ubiquitin-like modifier) regulates fundamental cellular processes and occurs through the sequential interactions and activities of three enzymes: E1, E2 and E3. SUMO E1 activates SUMO in a two-step process involving adenylation and thioester bond formation, followed by transfer of SUMO to its dedicated E2 enzyme, UBC9. This process is termed E1-E2 thioester transfer (or transthioesterification). Despite its fundamental importance, the molecular basis for SUMO E1-UBC9 thioester transfer and the molecular rules governing SUMO E1-UBC9 specificity are poorly understood. Here we present cryo-EM reconstructions of human SUMO E1 in complex with UBC9, SUMO1 adenylate and SUMO1 thioester intermediate. Our structures reveal drastic conformational changes that accompany thioester transfer, providing insights into the molecular recognition of UBC9 by SUMO E1 and delineating the rules that govern SUMO E1-UBC9 specificity. Collectively, our structural, biochemical and cell-based studies elucidate the molecular mechanisms by which SUMOylation exerts its essential biological functions.

PubMed: 40999065
DOI: 10.1038/s41594-025-01681-8

Experimental method

ELECTRON MICROSCOPY (2.7 Å)