5h07: Difference between revisions
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==TNIP2-Ub complex, C2 form== | |||
<StructureSection load='5h07' size='340' side='right' caption='[[5h07]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5h07]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H07 FirstGlance]. <br> | |||
</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=5h07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h07 OCA], [http://pdbe.org/5h07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h07 RCSB], [http://www.ebi.ac.uk/pdbsum/5h07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h07 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> [[http://www.uniprot.org/uniprot/TNIP2_HUMAN TNIP2_HUMAN]] Inhibits NF-kappa-B activation by blocking the interaction of RIPK1 with its downstream effector NEMO/IKBKG. Forms a ternary complex with NFKB1 and MAP3K8 but appears to function upstream of MAP3K8 in the TLR4 signaling pathway that regulates MAP3K8 activation. Involved in activation of the MEK/ERK signaling pathway during innate immune response; this function seems to be stimulus- and cell type specific. Required for stability of MAP3K8. Involved in regulation of apoptosis in endothelial cells; promotes TEK agonist-stimulated endothelial survival. May act as transcriptional coactivator when translocated to the nucleus. Enhances CHUK-mediated NF-kappa-B activation involving NF-kappa-B p50-p65 and p50-c-Rel complexes.<ref>PMID:12595760</ref> <ref>PMID:12753905</ref> <ref>PMID:12933576</ref> <ref>PMID:14653779</ref> <ref>PMID:15169888</ref> <ref>PMID:21784860</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-kappaB (NF-kappaB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-kappaB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration. Surprisingly, three ubiquitin units could form a right-handed helical trimer to bridge two ABIN2 dimers. The residues around the M1-linkage are crucial for ABIN2 to recognize tri-ubiquitin. The tri-ubiquitin bridging two ABIN2 dimers model suggests a possible higher-order signaling complex assembled between M1-linked polyubiquitinated proteins, ubiquitin-binding proteins, and effector signaling proteins in signal transduction. | |||
Structural Insights into Linear Tri-ubiquitin Recognition by A20-Binding Inhibitor of NF-kappaB, ABIN-2.,Lin SM, Lin SC, Hong JY, Su TW, Kuo BJ, Chang WH, Tu YF, Lo YC Structure. 2017 Jan 3;25(1):66-78. doi: 10.1016/j.str.2016.11.005. Epub 2016 Dec , 1. PMID:27916521<ref>PMID:27916521</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5h07" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lin, S C]] | |||
[[Category: Lo, Y C]] | |||
[[Category: Coiled-coil]] | |||
[[Category: Complex]] | |||
[[Category: Signal transduction]] | |||
[[Category: Signaling protein]] | |||
Revision as of 19:44, 9 March 2017
TNIP2-Ub complex, C2 formTNIP2-Ub complex, C2 form
Structural highlights
Function[UBC_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[1] [2] [TNIP2_HUMAN] Inhibits NF-kappa-B activation by blocking the interaction of RIPK1 with its downstream effector NEMO/IKBKG. Forms a ternary complex with NFKB1 and MAP3K8 but appears to function upstream of MAP3K8 in the TLR4 signaling pathway that regulates MAP3K8 activation. Involved in activation of the MEK/ERK signaling pathway during innate immune response; this function seems to be stimulus- and cell type specific. Required for stability of MAP3K8. Involved in regulation of apoptosis in endothelial cells; promotes TEK agonist-stimulated endothelial survival. May act as transcriptional coactivator when translocated to the nucleus. Enhances CHUK-mediated NF-kappa-B activation involving NF-kappa-B p50-p65 and p50-c-Rel complexes.[3] [4] [5] [6] [7] [8] Publication Abstract from PubMedRecognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-kappaB (NF-kappaB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-kappaB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration. Surprisingly, three ubiquitin units could form a right-handed helical trimer to bridge two ABIN2 dimers. The residues around the M1-linkage are crucial for ABIN2 to recognize tri-ubiquitin. The tri-ubiquitin bridging two ABIN2 dimers model suggests a possible higher-order signaling complex assembled between M1-linked polyubiquitinated proteins, ubiquitin-binding proteins, and effector signaling proteins in signal transduction. Structural Insights into Linear Tri-ubiquitin Recognition by A20-Binding Inhibitor of NF-kappaB, ABIN-2.,Lin SM, Lin SC, Hong JY, Su TW, Kuo BJ, Chang WH, Tu YF, Lo YC Structure. 2017 Jan 3;25(1):66-78. doi: 10.1016/j.str.2016.11.005. Epub 2016 Dec , 1. PMID:27916521[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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