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| | <StructureSection load='6uma' size='340' side='right'caption='[[6uma]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6uma' size='340' side='right'caption='[[6uma]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uma]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UMA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uma]] is a 2 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=6UMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UMA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 1.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6umb|6umb]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIM7, GNIP, RNF90 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6uma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uma OCA], [https://pdbe.org/6uma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uma RCSB], [https://www.ebi.ac.uk/pdbsum/6uma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uma 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=6uma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uma OCA], [https://pdbe.org/6uma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uma RCSB], [https://www.ebi.ac.uk/pdbsum/6uma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uma ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TRIM7_HUMAN TRIM7_HUMAN]] E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7]<ref>PMID:25851810</ref> <ref>PMID:32126128</ref> (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.<ref>PMID:32641828</ref>
| + | [https://www.uniprot.org/uniprot/TRIM7_HUMAN TRIM7_HUMAN] E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7]<ref>PMID:25851810</ref> <ref>PMID:32126128</ref> (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.<ref>PMID:32641828</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6uma" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6uma" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RING-type E3 ubiquitin transferase]]
| + | [[Category: Carrizo ME]] |
| - | [[Category: Carrizo, M E]] | + | [[Category: Munoz Sosa CJ]] |
| - | [[Category: Sosa, C J.Munoz]] | + | |
| - | [[Category: B30 2]]
| + | |
| - | [[Category: E3 ubiquitin ligase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Pry/spry]]
| + | |
| - | [[Category: Trim7]]
| + | |
| Structural highlights
Function
TRIM7_HUMAN E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7][1] [2] (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.[3]
Publication Abstract from PubMed
TRIM7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1, the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis, and thus represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal tripartite motif (TRIM) and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C-terminus. In order to contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7(B30.2)) in two crystal forms at resolutions of 1.6 A and 1.8 A. TRIM7(B30.2) exhibits the typical B30.2 domain fold, consisting of two antiparallel beta-sheets of seven and six strands, arranged as a distorted beta-sandwich. Furthermore, two long loops partially cover the concave face of the beta-sandwich defined by the beta-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for glycogenin-1. These studies showed that Leu423, Ser499 and Cys501 of TRIM7(B30.2), and the C-terminal 33 amino acids of glycogenin-1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7(B30.2)-glycogenin-1 C-terminal peptide complex. These data provide useful information that can be used to target this interaction for the development of potential therapeutic agents.
Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1.,Munoz Sosa CJ, Issoglio FM, Carrizo ME J Biol Chem. 2021 May 11:100772. doi: 10.1016/j.jbc.2021.100772. PMID:33989636[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chakraborty A, Diefenbacher ME, Mylona A, Kassel O, Behrens A. The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nat Commun. 2015 Apr 8;6:6782. doi: 10.1038/ncomms7782. PMID:25851810 doi:http://dx.doi.org/10.1038/ncomms7782
- ↑ Yang B, Liu Y, Cui Y, Song D, Zhang G, Ma S, Liu Y, Chen M, Chen F, Wang H, Wang J. RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation. PLoS Pathog. 2020 Mar 3;16(3):e1008387. doi: 10.1371/journal.ppat.1008387., eCollection 2020 Mar. PMID:32126128 doi:http://dx.doi.org/10.1371/journal.ppat.1008387
- ↑ Giraldo MI, Xia H, Aguilera-Aguirre L, Hage A, van Tol S, Shan C, Xie X, Sturdevant GL, Robertson SJ, McNally KL, Meade-White K, Azar SR, Rossi SL, Maury W, Woodson M, Ramage H, Johnson JR, Krogan NJ, Morais MC, Best SM, Shi PY, Rajsbaum R. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus. Nature. 2020 Sep;585(7825):414-419. doi: 10.1038/s41586-020-2457-8. Epub 2020 Jul, 8. PMID:32641828 doi:http://dx.doi.org/10.1038/s41586-020-2457-8
- ↑ Munoz Sosa CJ, Issoglio FM, Carrizo ME. Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1. J Biol Chem. 2021 May 11:100772. doi: 10.1016/j.jbc.2021.100772. PMID:33989636 doi:http://dx.doi.org/10.1016/j.jbc.2021.100772
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