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| | ==DCNL complex with N-terminally acetylated NEDD8 E2 peptide== | | ==DCNL complex with N-terminally acetylated NEDD8 E2 peptide== |
| - | <StructureSection load='4gao' size='340' side='right' caption='[[4gao]], [[Resolution|resolution]] 3.28Å' scene=''> | + | <StructureSection load='4gao' size='340' side='right'caption='[[4gao]], [[Resolution|resolution]] 3.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gao]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GAO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gao]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AME:N-ACETYLMETHIONINE'>AME</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AME:N-ACETYLMETHIONINE'>AME</scene></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=4gao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gao OCA], [https://pdbe.org/4gao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gao RCSB], [https://www.ebi.ac.uk/pdbsum/4gao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gao ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gba|4gba]]</td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCUN1D2, C13orf17, DCUN1L2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4gao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gao OCA], [http://pdbe.org/4gao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gao RCSB], [http://www.ebi.ac.uk/pdbsum/4gao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gao ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCNL2_HUMAN DCNL2_HUMAN]] Potently stimulates the neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes from the NEDD8-conjugating E2 enzyme UBC12. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity.<ref>PMID:23201271</ref> [[http://www.uniprot.org/uniprot/UBC12_HUMAN UBC12_HUMAN]] Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation.<ref>PMID:10207026</ref> <ref>PMID:15361859</ref> | + | [https://www.uniprot.org/uniprot/DCNL2_HUMAN DCNL2_HUMAN] Potently stimulates the neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes from the NEDD8-conjugating E2 enzyme UBC12. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity.<ref>PMID:23201271</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 conjugating enzyme|Ubiquitin conjugating enzyme]] | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bennett, E J]] | + | [[Category: Large Structures]] |
| - | [[Category: Harper, J W]] | + | [[Category: Bennett EJ]] |
| - | [[Category: Miller, D J]] | + | [[Category: Harper JW]] |
| - | [[Category: Monda, J K]] | + | [[Category: Miller DJ]] |
| - | [[Category: Schulman, B A]] | + | [[Category: Monda JK]] |
| - | [[Category: Scott, D C]] | + | [[Category: Schulman BA]] |
| - | [[Category: E3 ligase]] | + | [[Category: Scott DC]] |
| - | [[Category: Ligase-peptide complex]]
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| Structural highlights
Function
DCNL2_HUMAN Potently stimulates the neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes from the NEDD8-conjugating E2 enzyme UBC12. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity.[1]
Publication Abstract from PubMed
Little is known about molecular recognition of acetylated N termini, despite prevalence of this modification among eukaryotic cytosolic proteins. We report that the family of human DCN-like (DCNL) co-E3s, which promote ligation of the ubiquitin-like protein NEDD8 to cullin targets, recognizes acetylated N termini of the E2 enzymes UBC12 and UBE2F. Systematic biochemical and biophysical analyses reveal 40- and 10-fold variations in affinities among different DCNL-cullin and DCNL-E2 complexes, contributing to varying efficiencies of different NEDD8 ligation cascades. Structures of DCNL2 and DCNL3 complexes with N-terminally acetylated peptides from UBC12 and UBE2F illuminate a common mechanism by which DCNL proteins recognize N-terminally acetylated E2s and how selectivity for interactions dependent on N-acetyl-methionine are established through side chains recognizing distal residues. Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1 protein, suggest it may be possible to develop small molecules blocking specific N-acetyl-methionine-dependent protein interactions.
Structural Conservation of Distinctive N-terminal Acetylation-Dependent Interactions across a Family of Mammalian NEDD8 Ligation Enzymes.,Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA Structure. 2012 Nov 27. pii: S0969-2126(12)00409-1. doi:, 10.1016/j.str.2012.10.013. PMID:23201271[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA. Structural Conservation of Distinctive N-terminal Acetylation-Dependent Interactions across a Family of Mammalian NEDD8 Ligation Enzymes. Structure. 2012 Nov 27. pii: S0969-2126(12)00409-1. doi:, 10.1016/j.str.2012.10.013. PMID:23201271 doi:http://dx.doi.org/10.1016/j.str.2012.10.013
- ↑ Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA. Structural Conservation of Distinctive N-terminal Acetylation-Dependent Interactions across a Family of Mammalian NEDD8 Ligation Enzymes. Structure. 2012 Nov 27. pii: S0969-2126(12)00409-1. doi:, 10.1016/j.str.2012.10.013. PMID:23201271 doi:http://dx.doi.org/10.1016/j.str.2012.10.013
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