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| | ==NMR based structural model of the UBCH8-UBIQUITIN complex== | | ==NMR based structural model of the UBCH8-UBIQUITIN complex== |
| - | <StructureSection load='2kjh' size='340' side='right'caption='[[2kjh]], [[NMR_Ensembles_of_Models | 16 NMR models]]' scene=''> | + | <StructureSection load='2kjh' size='340' side='right'caption='[[2kjh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kjh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KJH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kjh]] is a 2 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=2KJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KJH FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wzv|1wzv]], [[1ubq|1ubq]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 16 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2L6, UBCH8 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPS27A UBA80, UBCEP1, UBA52, UBB, UBC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </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=2kjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kjh OCA], [https://pdbe.org/2kjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kjh RCSB], [https://www.ebi.ac.uk/pdbsum/2kjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kjh 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=2kjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kjh OCA], [https://pdbe.org/2kjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kjh RCSB], [https://www.ebi.ac.uk/pdbsum/2kjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kjh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/UB2L6_HUMAN UB2L6_HUMAN]] Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3.<ref>PMID:15131269</ref> <ref>PMID:16428300</ref> <ref>PMID:20508617</ref>
| + | [https://www.uniprot.org/uniprot/UB2L6_HUMAN UB2L6_HUMAN] Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3.<ref>PMID:15131269</ref> <ref>PMID:16428300</ref> <ref>PMID:20508617</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kj/2kjh_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kj/2kjh_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitin--protein ligase]]
| + | [[Category: Serniwka SA]] |
| - | [[Category: Serniwka, S A]] | + | [[Category: Shaw GS]] |
| - | [[Category: Shaw, G S]] | + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: E2 enzyme]]
| + | |
| - | [[Category: Haddock model]]
| + | |
| - | [[Category: Isopeptide bond]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ligase-protein binding complex]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| - | [[Category: Ubl conjugation]]
| + | |
| - | [[Category: Ubl conjugation pathway]]
| + | |
| Structural highlights
Function
UB2L6_HUMAN Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3.[1] [2] [3]
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-mediated proteolysis utilizes a series of three key enzymes (E1, E2, and E3) to transfer and then covalently modify a substrate with ubiquitin. E2 conjugating enzymes are central proteins in this pathway responsible for the acceptance of a ubiquitin from the E1 enzyme and association with an E3 protein. All E2 enzymes covalently bind ubiquitin through a thiolester linkage between a conserved active-site cysteine on E2 and the C-terminal glycine on ubiquitin. It is not known whether E2 enzymes utilize similar surfaces and residues to coordinate a ubiquitin molecule and how this might contribute to any substrate specificity. In this work, we determined the structure of the human E2 enzyme UbcH8 (UBE2L6) covalently bound to ubiquitin by NMR spectroscopy. A disulfide bond mimicking the short-lived thiolester was formed between the two proteins providing a stable complex. Overall, the structure of UbcH8 does not undergo a significant conformational change upon forming a complex with ubiquitin. Chemical shift perturbation and cross-saturation experiments were used to identify contacts between UbcH8 and ubiquitin and those contacts used as inputs for HADDOCK molecular docking to produce the structure of the UbcH8-ubiquitin complex. An ensemble of 16 structures (root-mean-square deviation of 0.83 A) showed that ubiquitin interacts with the linker region prior to the alpha5 helix as well as residues near the catalytic site. This region corresponds to an area of negative potential on the UbcH8 surface and is considerably different from other E2-ubiquitin interaction sites. Our findings indicate the positioning of ubiquitin on UbcH8 would still allow interaction with E1 and E3 enzymes. Together, the results suggest the UbcH8-ubiquitin complex may provide an additional level of specificity in the ubiquitination pathway.
The Structure of the UbcH8-Ubiquitin Complex Shows a Unique Ubiquitin Interaction Site.,Serniwka SA, Shaw GS Biochemistry. 2009 Dec 4. PMID:19928833[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhao C, Beaudenon SL, Kelley ML, Waddell MB, Yuan W, Schulman BA, Huibregtse JM, Krug RM. The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7578-82. Epub 2004 May 6. PMID:15131269 doi:http://dx.doi.org/10.1073/pnas.0402528101
- ↑ Takeuchi T, Iwahara S, Saeki Y, Sasajima H, Yokosawa H. Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme. J Biochem. 2005 Dec;138(6):711-9. PMID:16428300 doi:10.1093/jb/mvi172
- ↑ Buchwald M, Pietschmann K, Muller JP, Bohmer FD, Heinzel T, Kramer OH. Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation. Leukemia. 2010 Aug;24(8):1412-21. doi: 10.1038/leu.2010.114. Epub 2010 May 27. PMID:20508617 doi:10.1038/leu.2010.114
- ↑ Serniwka SA, Shaw GS. The Structure of the UbcH8-Ubiquitin Complex Shows a Unique Ubiquitin Interaction Site. Biochemistry. 2009 Dec 4. PMID:19928833 doi:10.1021/bi901686j
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