| Structural highlights
Function
[UBA5_HUMAN] E1-like enzyme which activates UFM1 and SUMO2.[1] [2] [3] [UFM1_HUMAN] Ubiquitin-like modifier protein which binds to a number of target proteins, such as DDRGK1.[4] [5]
Publication Abstract from PubMed
Modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is a critical cellular process implicated in a variety of cellular states and outcomes. A prerequisite for target protein modification by a UBL is the activation of the latter by activating enzymes (E1s). Here, we present the crystal structure of the non-canonical homodimeric E1, UBA5, in complex with its cognate UBL, UFM1, and supporting biochemical experiments. We find that UBA5 binds to UFM1 via a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 dimer. This binding mechanism requires a region C-terminal to the adenylation domain that brings UFM1 to the active site of the adjacent UBA5 subunit. We also find that transfer of UFM1 from UBA5 to the E2, UFC1, occurs via a trans mechanism, thereby requiring a homodimer of UBA5. These findings explicitly elucidate the role of UBA5 dimerization in UFM1 activation.
Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex.,Oweis W, Padala P, Hassouna F, Cohen-Kfir E, Gibbs DR, Todd EA, Berndsen CE, Wiener R Cell Rep. 2016 Sep 20;16(12):3113-20. doi: 10.1016/j.celrep.2016.08.067. PMID:27653677[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E, Natsume T, Tanaka K. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J. 2004 May 5;23(9):1977-86. Epub 2004 Apr 8. PMID:15071506 doi:https://dx.doi.org/10.1038/sj.emboj.7600205
- ↑ Zheng M, Gu X, Zheng D, Yang Z, Li F, Zhao J, Xie Y, Ji C, Mao Y. UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins. J Cell Biochem. 2008 Aug 15;104(6):2324-34. doi: 10.1002/jcb.21791. PMID:18442052 doi:https://dx.doi.org/10.1002/jcb.21791
- ↑ Bacik JP, Walker JR, Ali M, Schimmer AD, Dhe-Paganon S. Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme. J Biol Chem. 2010 Jun 25;285(26):20273-80. Epub 2010 Apr 5. PMID:20368332 doi:10.1074/jbc.M110.102921
- ↑ Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E, Natsume T, Tanaka K. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J. 2004 May 5;23(9):1977-86. Epub 2004 Apr 8. PMID:15071506 doi:https://dx.doi.org/10.1038/sj.emboj.7600205
- ↑ Tatsumi K, Sou YS, Tada N, Nakamura E, Iemura S, Natsume T, Kang SH, Chung CH, Kasahara M, Kominami E, Yamamoto M, Tanaka K, Komatsu M. A novel type of E3 ligase for the Ufm1 conjugation system. J Biol Chem. 2010 Feb 19;285(8):5417-27. doi: 10.1074/jbc.M109.036814. Epub 2009 , Dec 14. PMID:20018847 doi:https://dx.doi.org/10.1074/jbc.M109.036814
- ↑ Oweis W, Padala P, Hassouna F, Cohen-Kfir E, Gibbs DR, Todd EA, Berndsen CE, Wiener R. Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex. Cell Rep. 2016 Sep 20;16(12):3113-20. doi: 10.1016/j.celrep.2016.08.067. PMID:27653677 doi:https://dx.doi.org/10.1016/j.celrep.2016.08.067
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