TY  - JOUR
A1  - Wesch, Nicole
A1  - Löhr, Frank
A1  - Rogova, Natalia
A1  - Dötsch, Volker
A1  - Rogov, Vladimir V.
T1  - A concerted action of UBA5 C-terminal unstructured regions is important for transfer of activated UFM1 to UFC1
T2  - International journal of molecular sciences
N2  - Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.
KW  - UFM1
KW  - UBA5
KW  - UFC1
KW  - protein-protein interactions
KW  - NMR
KW  - complex structure
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61810
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-618101
SN  - 1422-0067
VL  - 22
IS  - 14, art. 7390
SP  - 1
EP  - 19
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -