5kni

Crystal Structure of the wild-type SAM domain of human Tankyrase-1Crystal Structure of the wild-type SAM domain of human Tankyrase-1

Structural highlights

5kni is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TNKS1_HUMAN 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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Tankyrase-1 (TNKS1/PARP-5a) is a poly(ADP-ribose) polymerase (PARP) enzyme that regulates multiple cellular processes creating a poly(ADP-ribose) posttranslational modification that can lead to target protein turnover. TNKS1 thereby controls protein levels of key components of signaling pathways, including Axin1, the limiting component of the destruction complex in canonical Wnt signaling that degrades beta-catenin to prevent its coactivator function in gene expression. There are limited molecular level insights into TNKS1 regulation in cell signaling pathways. TNKS1 has a sterile alpha motif (SAM) domain that is known to mediate polymerization, but the functional requirement for SAM polymerization has not been assessed. We have determined the crystal structure of wild-type human TNKS1 SAM domain and used structure-based mutagenesis to disrupt polymer formation and assess the consequences on TNKS1 regulation of beta-catenin-dependent transcription. Our data indicate the SAM polymer is critical for TNKS1 catalytic activity and allows TNKS1 to efficiently access cytoplasmic signaling complexes.

Tankyrase Sterile alpha Motif Domain Polymerization Is Required for Its Role in Wnt Signaling.,Riccio AA, McCauley M, Langelier MF, Pascal JM Structure. 2016 Sep 6;24(9):1573-1581. doi: 10.1016/j.str.2016.06.022. Epub 2016 , Aug 4. PMID:27499439^[7]

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

References

↑ Chi NW, Lodish HF. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J Biol Chem. 2000 Dec 8;275(49):38437-44. PMID:10988299 doi:10.1074/jbc.M007635200
↑ Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332-42. PMID:11739745
↑ Chang W, Dynek JN, Smith S. NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis. Biochem J. 2005 Oct 15;391(Pt 2):177-84. PMID:16076287 doi:10.1042/BJ20050885
↑ Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16. PMID:19759537 doi:10.1038/nature08356
↑ Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang SM, Cong F. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011 May;13(5):623-9. doi: 10.1038/ncb2222. Epub 2011 Apr 10. PMID:21478859 doi:10.1038/ncb2222
↑ Ozaki Y, Matsui H, Asou H, Nagamachi A, Aki D, Honda H, Yasunaga S, Takihara Y, Yamamoto T, Izumi S, Ohsugi M, Inaba T. Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation. Mol Cell. 2012 Sep 14;47(5):694-706. doi: 10.1016/j.molcel.2012.06.033. Epub 2012, Aug 2. PMID:22864114 doi:10.1016/j.molcel.2012.06.033
↑ Riccio AA, McCauley M, Langelier MF, Pascal JM. Tankyrase Sterile alpha Motif Domain Polymerization Is Required for Its Role in Wnt Signaling. Structure. 2016 Sep 6;24(9):1573-1581. doi: 10.1016/j.str.2016.06.022. Epub 2016 , Aug 4. PMID:27499439 doi:http://dx.doi.org/10.1016/j.str.2016.06.022

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OCA

[1] Chi NW, Lodish HF. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J Biol Chem. 2000 Dec 8;275(49):38437-44. PMID:10988299 doi:10.1074/jbc.M007635200

[2] Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332-42. PMID:11739745

[3] Chang W, Dynek JN, Smith S. NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis. Biochem J. 2005 Oct 15;391(Pt 2):177-84. PMID:16076287 doi:10.1042/BJ20050885

[4] Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16. PMID:19759537 doi:10.1038/nature08356

[5] Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang SM, Cong F. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011 May;13(5):623-9. doi: 10.1038/ncb2222. Epub 2011 Apr 10. PMID:21478859 doi:10.1038/ncb2222

[6] Ozaki Y, Matsui H, Asou H, Nagamachi A, Aki D, Honda H, Yasunaga S, Takihara Y, Yamamoto T, Izumi S, Ohsugi M, Inaba T. Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation. Mol Cell. 2012 Sep 14;47(5):694-706. doi: 10.1016/j.molcel.2012.06.033. Epub 2012, Aug 2. PMID:22864114 doi:10.1016/j.molcel.2012.06.033

[7] Riccio AA, McCauley M, Langelier MF, Pascal JM. Tankyrase Sterile alpha Motif Domain Polymerization Is Required for Its Role in Wnt Signaling. Structure. 2016 Sep 6;24(9):1573-1581. doi: 10.1016/j.str.2016.06.022. Epub 2016 , Aug 4. PMID:27499439 doi:http://dx.doi.org/10.1016/j.str.2016.06.022

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