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| | ==E2 binding surface on Uba3 beta-grasp domain undergoes a conformational transition== | | ==E2 binding surface on Uba3 beta-grasp domain undergoes a conformational transition== |
| - | <StructureSection load='2lq7' size='340' side='right' caption='[[2lq7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lq7' size='340' side='right'caption='[[2lq7]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lq7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LQ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LQ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lq7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LQ7 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBA3, UBE1C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lq7 OCA], [http://pdbe.org/2lq7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lq7 RCSB], [http://www.ebi.ac.uk/pdbsum/2lq7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lq7 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lq7 OCA], [https://pdbe.org/2lq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lq7 RCSB], [https://www.ebi.ac.uk/pdbsum/2lq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lq7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBA3_HUMAN UBA3_HUMAN]] Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.<ref>PMID:10207026</ref> <ref>PMID:9694792</ref> <ref>PMID:12740388</ref> | + | [https://www.uniprot.org/uniprot/UBA3_HUMAN UBA3_HUMAN] Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.<ref>PMID:10207026</ref> <ref>PMID:9694792</ref> <ref>PMID:12740388</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin activating enzyme|Ubiquitin activating enzyme]] | + | *[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Elgin, E S]] | + | [[Category: Large Structures]] |
| - | [[Category: Peterson, F C]] | + | [[Category: Elgin ES]] |
| - | [[Category: Volkman, B F]] | + | [[Category: Peterson FC]] |
| - | [[Category: Beta grasp domain]] | + | [[Category: Volkman BF]] |
| - | [[Category: E1 enzyme]]
| + | |
| - | [[Category: Ligase]]
| + | |
| Structural highlights
Function
UBA3_HUMAN Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.[1] [2] [3]
Publication Abstract from PubMed
The covalent attachment of ubiquitin (Ub) and ubiquitin-like (Ubl) proteins to various eukaryotic targets plays critical roles in regulating numerous cellular processes. E1-activating enzymes are critical, because they catalyze activation of their cognate Ub/Ubl protein and are responsible for its transfer to the correct E2-conjugating enzyme(s). The activating enzyme for neural-precursor-cell-expressed developmentally downregulated 8 (NEDD8) is a heterodimer composed of APPBP1 and Uba3 subunits. The carboxyl terminal ubiquitin-like beta-grasp domain of human Uba3 (Uba3-betaGD) has been suggested as a key E2-binding site defining E2 specificity. In crystal structures of free E1 and the NEDD8-E1 complex, the E2-binding surface on the domain was missing from the electron density. However, when complexed with various E2s, this missing segment adopts a kinked alpha-helix. Here, we demonstrate that Uba3-betaGD is an independently folded domain in solution and that residues involved in E2 binding are absent from the NMR spectrum, indicating that the E2-binding surface on Uba3-betaGD interconverts between multiple conformations, analogous to a similar conformational transition observed in the E2-binding surface of SUMO E1. These results suggest that access to multiple conformational substates is an important feature of the E1-E2 interaction.
E2-binding surface on Uba3 beta-grasp domain undergoes a conformational transition.,Elgin ES, Sokmen N, Peterson FC, Volkman BF, Dag C, Haas AL Proteins. 2012 Oct;80(10):2482-7. doi: 10.1002/prot.24148. Epub 2012 Jul 31. PMID:22821745[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999 Apr 23;274(17):12036-42. PMID:10207026
- ↑ Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998 Aug 1;12(15):2263-8. PMID:9694792
- ↑ Bohnsack RN, Haas AL. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J Biol Chem. 2003 Jul 18;278(29):26823-30. Epub 2003 May 10. PMID:12740388 doi:10.1074/jbc.M303177200
- ↑ Elgin ES, Sokmen N, Peterson FC, Volkman BF, Dag C, Haas AL. E2-binding surface on Uba3 beta-grasp domain undergoes a conformational transition. Proteins. 2012 Oct;80(10):2482-7. doi: 10.1002/prot.24148. Epub 2012 Jul 31. PMID:22821745 doi:10.1002/prot.24148
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