All ubiquitin-like proteins (UBLs) undergo an activation process before their conjugation to target proteins. Although the steps required for the activation of UBLs are conserved and common to all UBLs, we have previously shown that the activation of the UBL, ubiquitin fold modifier 1 (UFM1) by the E1, Ufm1 modifier-activating enzyme 5 (UBA5) is executed in a trans-binding mechanism, not observed in any other E1. In this study, we explored the necessity of that mechanism for UFM1 activation and found that it is needed not only for UFM1 binding to UBA5 but also for stabilizing the UBA5 homodimer. Although UBA5 functions as a dimer, in solution it behaves as a weak dimer. Dimerization ofUBA5is required for ATP binding; therefore, stabilization of the dimer by UFM1enhances ATP binding. Our results make a connection between the binding ofUFM1toUBA5and the latter's affinity to ATP, so we propose a novel mechanism for the regulation of ATP's binding to E1.
Bibliographical noteFunding Information:
This work was supported by United States–Israel Binational Science Foundation (Grant 2013261), the Marie Curie Career Integration (Grant PCIG13-GA-2013-630755), and the Israel Science Foundation (Grant 1383/17). The authors declare no conflicts of interest.
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- Activating enzyme E1
- Ubiquitin-like protein