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Crystal structure of UBA5 fragment fused to the N-terminus of UFC1
Structural highlights
FunctionUBA5_HUMAN E1-like enzyme which activates UFM1 and SUMO2.[1] [2] [3] UFC1_HUMAN E2-like enzyme which forms an intermediate with UFM1 via a thioester linkage.[4] Publication Abstract from PubMedUfmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1's active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1's conjugation machinery and may serve as a basis for the development of ufmylation inhibitors. Structural basis for UFM1 transfer from UBA5 to UFC1.,Kumar M, Padala P, Fahoum J, Hassouna F, Tsaban T, Zoltsman G, Banerjee S, Cohen-Kfir E, Dessau M, Rosenzweig R, Isupov MN, Schueler-Furman O, Wiener R Nat Commun. 2021 Sep 29;12(1):5708. doi: 10.1038/s41467-021-25994-6. PMID:34588452[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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