TY  - JOUR
A1  - Truongvan, Ngoc
A1  - Li, Shurong
A1  - Misra, Mohit
A1  - Kuhn, Monika
A1  - Schindelin, Hermann
T1  - Structures of UBA6 explain its dual specificity for ubiquitin and FAT10
JF  - Nature Communications
N2  - The covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings.
KW  - enzyme mechanisms
KW  - post-translational modifications
KW  - X-ray crystallography
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301161
VL  - 13
ER  -