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| | ==TRIM32 RING== | | ==TRIM32 RING== |
| - | <StructureSection load='5fey' size='340' side='right' caption='[[5fey]], [[Resolution|resolution]] 2.23Å' scene=''> | + | <StructureSection load='5fey' size='340' side='right'caption='[[5fey]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fey]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FEY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fey]] 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=5FEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FEY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.23Å</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=5fey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fey OCA], [http://pdbe.org/5fey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fey RCSB], [http://www.ebi.ac.uk/pdbsum/5fey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fey ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5fey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fey OCA], [https://pdbe.org/5fey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fey RCSB], [https://www.ebi.ac.uk/pdbsum/5fey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fey ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TRI32_HUMAN TRI32_HUMAN]] Defects in TRIM32 are the cause of limb-girdle muscular dystrophy type 2H (LGMD2H) [MIM:[http://omim.org/entry/254110 254110]]; also known as muscular dystrophy Hutterite type. LGMD2H is an autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.<ref>PMID:11822024</ref> <ref>PMID:17994549</ref> Defects in TRIM32 are the cause of Bardet-Biedl syndrome type 11 (BBS11) [MIM:[http://omim.org/entry/209900 209900]]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.<ref>PMID:16606853</ref> | + | [https://www.uniprot.org/uniprot/TRI32_HUMAN TRI32_HUMAN] Defects in TRIM32 are the cause of limb-girdle muscular dystrophy type 2H (LGMD2H) [MIM:[https://omim.org/entry/254110 254110]; also known as muscular dystrophy Hutterite type. LGMD2H is an autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.<ref>PMID:11822024</ref> <ref>PMID:17994549</ref> Defects in TRIM32 are the cause of Bardet-Biedl syndrome type 11 (BBS11) [MIM:[https://omim.org/entry/209900 209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.<ref>PMID:16606853</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRI32_HUMAN TRI32_HUMAN]] Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo.<ref>PMID:19349376</ref> | + | [https://www.uniprot.org/uniprot/TRI32_HUMAN TRI32_HUMAN] Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo.<ref>PMID:19349376</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 protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Esposito, D]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Koliopoulos, M G]] | + | [[Category: Large Structures]] |
| - | [[Category: Rittinger, K]] | + | [[Category: Esposito D]] |
| - | [[Category: E3 ligase]] | + | [[Category: Koliopoulos MG]] |
| - | [[Category: Ligase]] | + | [[Category: Rittinger K]] |
| - | [[Category: Ubiquitin]]
| + | |
| Structural highlights
Disease
TRI32_HUMAN Defects in TRIM32 are the cause of limb-girdle muscular dystrophy type 2H (LGMD2H) [MIM:254110; also known as muscular dystrophy Hutterite type. LGMD2H is an autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.[1] [2] Defects in TRIM32 are the cause of Bardet-Biedl syndrome type 11 (BBS11) [MIM:209900. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.[3]
Function
TRI32_HUMAN Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo.[4]
Publication Abstract from PubMed
TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function.
Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity.,Koliopoulos MG, Esposito D, Christodoulou E, Taylor IA, Rittinger K EMBO J. 2016 May 6. pii: e201593741. PMID:27154206[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K. Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am J Hum Genet. 2002 Mar;70(3):663-72. Epub 2002 Jan 29. PMID:11822024 doi:S0002-9297(07)60269-9
- ↑ Saccone V, Palmieri M, Passamano L, Piluso G, Meroni G, Politano L, Nigro V. Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Hum Mutat. 2008 Feb;29(2):240-7. PMID:17994549 doi:10.1002/humu.20633
- ↑ Chiang AP, Beck JS, Yen HJ, Tayeh MK, Scheetz TE, Swiderski RE, Nishimura DY, Braun TA, Kim KY, Huang J, Elbedour K, Carmi R, Slusarski DC, Casavant TL, Stone EM, Sheffield VC. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11). Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6287-92. Epub 2006 Apr 10. PMID:16606853 doi:10.1073/pnas.0600158103
- ↑ Locke M, Tinsley CL, Benson MA, Blake DJ. TRIM32 is an E3 ubiquitin ligase for dysbindin. Hum Mol Genet. 2009 Jul 1;18(13):2344-58. doi: 10.1093/hmg/ddp167. Epub 2009 Apr , 6. PMID:19349376 doi:10.1093/hmg/ddp167
- ↑ Koliopoulos MG, Esposito D, Christodoulou E, Taylor IA, Rittinger K. Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity. EMBO J. 2016 May 6. pii: e201593741. PMID:27154206 doi:http://dx.doi.org/10.15252/embj.201593741
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