4tkp
From Proteopedia
(Difference between revisions)
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==Complex of Ubc13 with the RING domain of the TRIM5alpha retroviral restriction factor== | ==Complex of Ubc13 with the RING domain of the TRIM5alpha retroviral restriction factor== | ||
| - | <StructureSection load='4tkp' size='340' side='right' caption='[[4tkp]], [[Resolution|resolution]] 2.08Å' scene=''> | + | <StructureSection load='4tkp' size='340' side='right'caption='[[4tkp]], [[Resolution|resolution]] 2.08Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4tkp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TKP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TKP FirstGlance]. <br> | <table><tr><td colspan='2'>[[4tkp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TKP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TKP FirstGlance]. <br> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> [[http://www.uniprot.org/uniprot/TRIM5_MACMU TRIM5_MACMU]] Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm).<ref>PMID:21734049</ref> <ref>PMID:21035162</ref> <ref>PMID:22291694</ref> | [[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> [[http://www.uniprot.org/uniprot/TRIM5_MACMU TRIM5_MACMU]] Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm).<ref>PMID:21734049</ref> <ref>PMID:21035162</ref> <ref>PMID:22291694</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5alpha retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5alpha:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5alpha RING domain. Our data explain how higher-order oligomerization of TRIM5alpha, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5alpha and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection. | ||
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| + | RING Dimerization Links Higher-Order Assembly of TRIM5alpha to Synthesis of K63-Linked Polyubiquitin.,Yudina Z, Roa A, Johnson R, Biris N, de Souza Aranha Vieira DA, Tsiperson V, Reszka N, Taylor AB, Hart PJ, Demeler B, Diaz-Griffero F, Ivanov DN Cell Rep. 2015 Aug 4;12(5):788-97. doi: 10.1016/j.celrep.2015.06.072. Epub 2015, Jul 23. PMID:26212332<ref>PMID:26212332</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4tkp" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Macmu]] | [[Category: Macmu]] | ||
[[Category: Ubiquitin--protein ligase]] | [[Category: Ubiquitin--protein ligase]] | ||
Revision as of 07:02, 4 March 2020
Complex of Ubc13 with the RING domain of the TRIM5alpha retroviral restriction factor
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