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| | <StructureSection load='6n6s' size='340' side='right'caption='[[6n6s]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6n6s' size='340' side='right'caption='[[6n6s]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n6s]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N6S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n6s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N6S FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tnip1, Abin, Naf1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 3Å</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=6n6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n6s OCA], [http://pdbe.org/6n6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n6s RCSB], [http://www.ebi.ac.uk/pdbsum/6n6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n6s 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=6n6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n6s OCA], [https://pdbe.org/6n6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n6s RCSB], [https://www.ebi.ac.uk/pdbsum/6n6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n6s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNIP1_MOUSE TNIP1_MOUSE]] Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases.<ref>PMID:12586352</ref> <ref>PMID:21606507</ref> <ref>PMID:22011580</ref> | + | [https://www.uniprot.org/uniprot/TNIP1_MOUSE TNIP1_MOUSE] Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases.<ref>PMID:12586352</ref> <ref>PMID:21606507</ref> <ref>PMID:22011580</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of UBAN/di-Ub binding stoichiometry. Analysis of UBAN/M1-linked di-Ub binding characteristics indicates that phosphorylated S473 in OPTN and its corresponding phospho-mimetic residue in ABIN-1 (E484) are essential for high affinity interactions with M1-linked Ub chains. Also, a phospho-mimetic mutation of A303 in NEMO, corresponding to S473 of OPTN, increases binding affinity for M1-linked Ub chains. These findings are in line with the diverse physiological roles of UBAN domains, as phosphorylation of OPTN UBAN is required to enhance its binding to Ub during mitophagy.
| + | |
| - | | + | |
| - | Molecular Recognition of M1-Linked Ubiquitin Chains by Native and Phosphorylated UBAN Domains.,Herhaus L, van den Bedem H, Tang S, Maslennikov I, Wakatsuki S, Dikic I, Rahighi S J Mol Biol. 2019 Jun 24. pii: S0022-2836(19)30376-6. doi:, 10.1016/j.jmb.2019.06.012. PMID:31247202<ref>PMID:31247202</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6n6s" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dikic, I]] | + | [[Category: Dikic I]] |
| - | [[Category: Rahighi, S]] | + | [[Category: Rahighi S]] |
| - | [[Category: Wakatsuki, S]] | + | [[Category: Wakatsuki S]] |
| - | [[Category: A20-binding protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Ubiquitin-binding domain]]
| + | |
| Structural highlights
Function
TNIP1_MOUSE Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases.[1] [2] [3]
References
- ↑ Heyninck K, Kreike MM, Beyaert R. Structure-function analysis of the A20-binding inhibitor of NF-kappa B activation, ABIN-1. FEBS Lett. 2003 Feb 11;536(1-3):135-40. doi: 10.1016/s0014-5793(03)00041-3. PMID:12586352 doi:http://dx.doi.org/10.1016/s0014-5793(03)00041-3
- ↑ Nanda SK, Venigalla RK, Ordureau A, Patterson-Kane JC, Powell DW, Toth R, Arthur JS, Cohen P. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011 Jun 6;208(6):1215-28. doi: 10.1084/jem.20102177. Epub 2011 May, 23. PMID:21606507 doi:10.1084/jem.20102177
- ↑ Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V, Hacker H. A20-binding inhibitor of NF-kappaB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein beta activation and protects from inflammatory disease. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):E998-1006. doi:, 10.1073/pnas.1106232108. Epub 2011 Oct 19. PMID:22011580 doi:http://dx.doi.org/10.1073/pnas.1106232108
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