| Structural highlights
Function
SAE2_HUMAN The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ubiquitin-like modifications, which are carried out by similar biochemical mechanisms, regulate nearly every aspect of cellular function. Despite the recent advancements in characterizing their enzymology, our knowledge about the dynamic processes of these modifications is still fragmentary. In this study, we have uncovered an intrinsic affinity between the SUMO E2 and the Cys domain of SUMO E1. NMR studies in combination with paramagnetic spin labeling demonstrate that this interaction is mediated by previously unknown interfaces on both E1 and E2 and places the two catalytic Cys residues of the two enzymes in close proximity. Site-directed mutagenesis and enzymatic assays indicate that the interaction is fundamentally important for the transfer of SUMO from E1 to E2. Results from this study suggest that the interaction between E2 and the Cys domain of E1 participates in guiding the E2's translocation to E1's enzymatic active site in ubiquitin-like modifications.
The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications.,Wang J, Hu W, Cai S, Lee B, Song J, Chen Y Mol Cell. 2007 Jul 20;27(2):228-37. PMID:17643372[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Azuma Y, Tan SH, Cavenagh MM, Ainsztein AM, Saitoh H, Dasso M. Expression and regulation of the mammalian SUMO-1 E1 enzyme. FASEB J. 2001 Aug;15(10):1825-7. PMID:11481243
- ↑ Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. PMID:11451954 doi:10.1074/jbc.M104214200
- ↑ Wang J, Lee B, Cai S, Fukui L, Hu W, Chen Y. Conformational transition associated with E1-E2 interaction in small ubiquitin-like modifications. J Biol Chem. 2009 Jul 24;284(30):20340-8. doi: 10.1074/jbc.M109.000257. Epub 2009, May 14. PMID:19443651 doi:10.1074/jbc.M109.000257
- ↑ Lois LM, Lima CD. Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J. 2005 Feb 9;24(3):439-51. Epub 2005 Jan 20. PMID:15660128
- ↑ Wang J, Hu W, Cai S, Lee B, Song J, Chen Y. The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications. Mol Cell. 2007 Jul 20;27(2):228-37. PMID:17643372 doi:http://dx.doi.org/10.1016/j.molcel.2007.05.023
- ↑ Olsen SK, Capili AD, Lu X, Tan DS, Lima CD. Active site remodelling accompanies thioester bond formation in the SUMO E1. Nature. 2010 Feb 18;463(7283):906-12. PMID:20164921 doi:10.1038/nature08765
- ↑ Wang J, Hu W, Cai S, Lee B, Song J, Chen Y. The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications. Mol Cell. 2007 Jul 20;27(2):228-37. PMID:17643372 doi:http://dx.doi.org/10.1016/j.molcel.2007.05.023
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