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| | <StructureSection load='3zkj' size='340' side='right'caption='[[3zkj]], [[Resolution|resolution]] 2.58Å' scene=''> | | <StructureSection load='3zkj' size='340' side='right'caption='[[3zkj]], [[Resolution|resolution]] 2.58Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zkj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2xai 2xai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zkj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2xai 2xai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.58Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wzk|2wzk]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=3zkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zkj OCA], [https://pdbe.org/3zkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zkj RCSB], [https://www.ebi.ac.uk/pdbsum/3zkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zkj 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=3zkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zkj OCA], [https://pdbe.org/3zkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zkj RCSB], [https://www.ebi.ac.uk/pdbsum/3zkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zkj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ASB9_HUMAN ASB9_HUMAN]] Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes at least two forms of creatine kinase, CKB and CKMT1A.<ref>PMID:20302626</ref> <ref>PMID:22418839</ref> [[https://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> [[https://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>
| + | [https://www.uniprot.org/uniprot/ASB9_HUMAN ASB9_HUMAN] Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes at least two forms of creatine kinase, CKB and CKMT1A.<ref>PMID:20302626</ref> <ref>PMID:22418839</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Ayinampudi, V]] | + | [[Category: Ayinampudi V]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Bullock, A N]] | + | [[Category: Bullock AN]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Edwards AM]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Filippakopoulos P]] |
| - | [[Category: Filippakopoulos, P]] | + | [[Category: Guo K]] |
| - | [[Category: Guo, K]] | + | [[Category: Keates T]] |
| - | [[Category: Keates, T]] | + | [[Category: Knapp S]] |
| - | [[Category: Knapp, S]] | + | [[Category: Krojer T]] |
| - | [[Category: Krojer, T]] | + | [[Category: Muniz JRC]] |
| - | [[Category: Muniz, J R.C]] | + | [[Category: Savitsky P]] |
| - | [[Category: Savitsky, P]] | + | [[Category: Ugochukwu E]] |
| - | [[Category: Ugochukwu, E]] | + | [[Category: Vollmar M]] |
| - | [[Category: Vollmar, M]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Yue WW]] |
| - | [[Category: Yue, W W]] | + | [[Category: Zhang Y]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Von Delft F]] |
| - | [[Category: Autoantibody]] | + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| Structural highlights
Function
ASB9_HUMAN Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes at least two forms of creatine kinase, CKB and CKMT1A.[1] [2]
Publication Abstract from PubMed
Multi-subunit Cullin-RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-containing ankyrin repeat proteins (ASB1-18), which assemble with Elongins B and C and Cul5. We determined the crystal structures of the ternary complex of ASB9-Elongin B/C as well as the interacting N-terminal domain of Cul5 and used structural comparisons to establish a model for the complete Cul5-based E3 ligase. The structures reveal a distinct architecture of the ASB9 complex that positions the ankyrin domain coaxial to the SOCS box-Elongin B/C complex and perpendicular to other repeat protein complexes. This alternative architecture appears favorable to present the ankyrin domain substrate-binding site to the E2-ubiquitin, while also providing spacing suitable for bulky ASB9 substrates, such as the creatine kinases. The presented Cul5 structure also differs from previous models and deviates from other Cullins via a rigid-body rotation between Cullin repeats. This work highlights the adaptability of repeat domain proteins as scaffolds in substrate recognition and lays the foundation for future structure-function studies of this important E3 family.
Molecular Architecture of the Ankyrin SOCS Box Family of Cul5-Dependent E3 Ubiquitin Ligases.,Muniz JR, Guo K, Kershaw NJ, Ayinampudi V, von Delft F, Babon JJ, Bullock AN J Mol Biol. 2013 Jun 25. pii: S0022-2836(13)00394-X. doi:, 10.1016/j.jmb.2013.06.015. PMID:23806657[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kwon S, Kim D, Rhee JW, Park JA, Kim DW, Kim DS, Lee Y, Kwon HJ. ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function. BMC Biol. 2010 Mar 19;8:23. doi: 10.1186/1741-7007-8-23. PMID:20302626 doi:10.1186/1741-7007-8-23
- ↑ Fei X, Gu X, Fan S, Yang Z, Li F, Zhang C, Gong W, Mao Y, Ji C. Crystal structure of Human ASB9-2 and substrate-recognition of CKB. Protein J. 2012 Apr;31(4):275-84. PMID:22418839 doi:10.1007/s10930-012-9401-1
- ↑ Muniz JR, Guo K, Kershaw NJ, Ayinampudi V, von Delft F, Babon JJ, Bullock AN. Molecular Architecture of the Ankyrin SOCS Box Family of Cul5-Dependent E3 Ubiquitin Ligases. J Mol Biol. 2013 Jun 25. pii: S0022-2836(13)00394-X. doi:, 10.1016/j.jmb.2013.06.015. PMID:23806657 doi:10.1016/j.jmb.2013.06.015
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