Structural basis for UFM1 transfer from UBA5 to UFC1.
Catalytic Domain
/ genetics
Humans
Molecular Docking Simulation
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
/ genetics
Protein Processing, Post-Translational
Proteins
/ genetics
Recombinant Proteins
/ genetics
Ubiquitin-Activating Enzymes
/ genetics
Ubiquitin-Conjugating Enzymes
/ genetics
X-Ray Diffraction
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 09 2021
29 09 2021
Historique:
received:
26
03
2021
accepted:
07
09
2021
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
24
10
2021
Statut:
epublish
Résumé
Ufmylation 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.
Identifiants
pubmed: 34588452
doi: 10.1038/s41467-021-25994-6
pii: 10.1038/s41467-021-25994-6
pmc: PMC8481289
doi:
Substances chimiques
Proteins
0
Recombinant Proteins
0
UBA5 protein, human
0
UFC1 protein, human
0
UFM1 protein, human
0
Ubiquitin-Conjugating Enzymes
EC 2.3.2.23
Ubiquitin-Activating Enzymes
EC 6.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5708Informations de copyright
© 2021. The Author(s).
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