3utm

From Proteopedia

(Difference between revisions)

Revision as of 08:05, 20 July 2022

Crystal structure of a mouse Tankyrase-Axin complex

Structural highlights

3utm is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	TANKRYASE1, Tnks, Tnks1 (LK3 transgenic mice), Axin, Axin1, Fu (LK3 transgenic mice)
Activity:	NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TNKS1_MOUSE] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1 (By similarity). [AXIN1_MOUSE] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Axin is a tumor suppressor and a key negative regulator of the Wnt/beta-catenin signaling pathway. Axin turnover is controlled by its poly-ADP-ribosylation catalyzed by tankyrase (TNKS), which requires the direct interaction of Axin with TNKS. This interaction is thus an attractive drug target for treating cancers, brain injuries, and other diseases where beta-catenin is involved. Here we report the crystal structure of a mouse TNKS1 fragment containing ankyrin-repeat clusters 2 and 3 (ARC2-3) in a complex with the TNKS-binding domain of mouse Axin1. Surprisingly, we found that Axin contains two discrete TNKS-binding segments, both of which bind simultaneously to the two ARC2 domains in the ARC2-3 homodimer. Our crystal structure shows that in each TNKS-binding segment of Axin there is a conserved glycine residue that lies in the bottom of a narrow "gate" formed by two parallel tyrosine side chains on the TNKS surface. This glycine-selection gate is crucial for TNKS-Axin interactions, as mutation of the TNKS gate-forming residues, or mutation of either glycine residue in the two Axin segments, completely abolishes the binding of the corresponding Axin segment to TNKS. The bivalent binding of Axin to TNKS is required for Axin turnover, since mutations in either gate-binding glycine residue in Axin lead to Axin stabilization in the cell. In addition, our analyses also reveal the structural basis for TNKS substrate recruitment, and shed light on the overall structure of TNKS that should help in developing specific inhibitors of Wnt/beta-catenin signaling.

Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment.,Morrone S, Cheng Z, Moon RT, Cong F, Xu W Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1500-5. Epub 2012 Jan 17. PMID:22307604^[4]

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

References

↑ Rui HL, Fan E, Zhou HM, Xu Z, Zhang Y, Lin SC. SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling. J Biol Chem. 2002 Nov 8;277(45):42981-6. Epub 2002 Sep 9. PMID:12223491 doi:http://dx.doi.org/10.1074/jbc.M208099200
↑ Rui Y, Xu Z, Lin S, Li Q, Rui H, Luo W, Zhou HM, Cheung PY, Wu Z, Ye Z, Li P, Han J, Lin SC. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation. EMBO J. 2004 Nov 24;23(23):4583-94. Epub 2004 Nov 4. PMID:15526030 doi:http://dx.doi.org/10.1038/sj.emboj.7600475
↑ Rui Y, Xu Z, Xiong B, Cao Y, Lin S, Zhang M, Chan SC, Luo W, Han Y, Lu Z, Ye Z, Zhou HM, Han J, Meng A, Lin SC. A beta-catenin-independent dorsalization pathway activated by Axin/JNK signaling and antagonized by aida. Dev Cell. 2007 Aug;13(2):268-82. PMID:17681137 doi:http://dx.doi.org/S1534-5807(07)00267-5
↑ Morrone S, Cheng Z, Moon RT, Cong F, Xu W. Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1500-5. Epub 2012 Jan 17. PMID:22307604 doi:http://dx.doi.org/10.1073/pnas.1116618109

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3utm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a mouse Tankyrase-Axin complex==
-<StructureSection load='3utm' size='340' side='right' caption='[[3utm]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3utm' size='340' side='right'caption='[[3utm]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3utm]] is a 3 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=3UTM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UTM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3utm]] is a 3 chain structure with sequence from [https://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=3UTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UTM FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TANKRYASE1, Tnks, Tnks1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Axin, Axin1, Fu ([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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TANKRYASE1, Tnks, Tnks1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Axin, Axin1, Fu ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=3utm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3utm OCA], [http://pdbe.org/3utm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3utm RCSB], [http://www.ebi.ac.uk/pdbsum/3utm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3utm 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=3utm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3utm OCA], [https://pdbe.org/3utm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3utm RCSB], [https://www.ebi.ac.uk/pdbsum/3utm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3utm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TNKS1_MOUSE TNKS1_MOUSE]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1 (By similarity). [[http://www.uniprot.org/uniprot/AXIN1_MOUSE AXIN1_MOUSE]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12223491</ref> <ref>PMID:15526030</ref> <ref>PMID:17681137</ref>
+[[https://www.uniprot.org/uniprot/TNKS1_MOUSE TNKS1_MOUSE]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1 (By similarity). [[https://www.uniprot.org/uniprot/AXIN1_MOUSE AXIN1_MOUSE]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12223491</ref> <ref>PMID:15526030</ref> <ref>PMID:17681137</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[Axin|Axin]]
+*[[Axin 3D structures|Axin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Cheng, Z]]

3utm

From Proteopedia

Revision as of 08:05, 20 July 2022

Crystal structure of a mouse Tankyrase-Axin complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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