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6n6r

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Revision as of 15:59, 28 August 2019

Crystal structure of ABIN-1 UBAN in complex with two M1-linked di-ubiquitins

Structural highlights

6n6r is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	UBC (HUMAN), Tnip1, Abin, Naf1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
↑ 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
↑ Herhaus L, van den Bedem H, Tang S, Maslennikov I, Wakatsuki S, Dikic I, Rahighi S. Molecular Recognition of M1-Linked Ubiquitin Chains by Native and Phosphorylated UBAN Domains. J Mol Biol. 2019 Jun 24. pii: S0022-2836(19)30376-6. doi:, 10.1016/j.jmb.2019.06.012. PMID:31247202 doi:http://dx.doi.org/10.1016/j.jmb.2019.06.012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6n6r"

@@ Line 3: / Line 3: @@
 <StructureSection load='6n6r' size='340' side='right'caption='[[6n6r]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6n6r]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N6R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6n6r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=6N6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N6R 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=6n6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n6r OCA], [http://pdbe.org/6n6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n6r RCSB], [http://www.ebi.ac.uk/pdbsum/6n6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n6r ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Tnip1, Abin, Naf1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6n6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n6r OCA], [http://pdbe.org/6n6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n6r RCSB], [http://www.ebi.ac.uk/pdbsum/6n6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n6r ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Dikic, I]]
 [[Category: Rahighi, S]]

6n6r

From Proteopedia

Revision as of 15:59, 28 August 2019

Crystal structure of ABIN-1 UBAN in complex with two M1-linked di-ubiquitins

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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