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Human Tankyrase-2, catalytic PARP domain

PDB Code 3KR7 Target Class Poly ADP-ribose polymerase Target Tankyrase-2 Alias PARP-5b, PARP-5c, PARP5B, PARP5C, TANK2, TNKL, TNKS2 Disease Area/Function cancer Date Deposited Nov 18 2009 Authors T.KARLBERG, P.SCHUTZ, C.H.ARROWSMITH, H.BERGLUND, C.BOUNTRA, R.COLLINS, A.M.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, A.JOHANSSON, I.JOHANSSON, A.KALLAS, T.KOTENYOVA, A.KOTZSCH, P.KRAULIS, T.K.NIELSEN, M.MOCHE, P.NORDLUND, T.NYMAN, C.PERSSON, M.I.SIPONEN, A.G.THORSELL, L.TRESAUGUES, S.VAN DEN BERG, J.WEIGELT, M.WELIN, M.WISNIEWSKA, H.SCHULER Related Structure 3KR8, 3MHK, 3MHJ

About this structure

Tankyrases are poly-ADP-ribose transferases. The two highly homologous tankyrase isoforms in human, TNKS1/PARP5a (1) and TNKS2/PARP5b (2-4), share an ankyrin repeat domain, a sterile alpha module (SAM) domain, and a C-terminal PARP catalytic domain, while the histidine, proline, and serine repeat domain near the N-terminus is present only in TNKS1. The PARP catalytic domains of TNKS1 (residues Q1091 – P1313) and TNKS2 (Q938 – P1160) are 86% identical and 95% similar.

Tankyrases are positive regulators of telomere elongation; they poly-ADP-ribosylate and displace TRF1 from telomeric repeats thereby allowing telomerase access to telomere ends (1, 5). Tankyrases have recently been discovered to play a key role in the Wnt signalling pathway (6).

Here we present the crystal structure of the human tankyrase-2 PARP domain in its apo form at 1.95Å. Crystals were obtained by in situ proteolysis (7). The structure is similar to the TNKS1 catalytic domain solved by us previously (pdb entry 2RF5 and ref. 8), except for a different conformation of the donor site loop (H1048-G1058).

References

  1. Smith S, Giriat I, Schmitt A and de Lange T (1998) Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484-1487. PubMed 9822378
  2. Kaminker PG et al. (2001) TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J. Biol. Chem. 276, 35891-35899. PubMed 11454873
  3. Amé JC et al. (2004) The PARP superfamily. Bioessays 26, 882-893. PubMed 15273990
  4. Hsiao SJ and Smith S (2008) Tankyrase function at telomeres, spindle poles, and beyond. Biochimie 90, 83-92. PubMed 17825467
  5. Smith S and de Lange T (1998) Tankyrase promotes telomere elongation in human cells. Curr. Biol. 10, 1299-1302. PubMed 11069113
  6. Huang SM et al. (2009) Tankyrase inhibition stabilizes axin and antagonizes Wnt signaling. Nature 461, 614-620. PubMed 19759537
  7. Wernimont A and Edwards A (2009) In situ proteolysis to generate crystals for structure determination: an update. PLoS One 4, e5094. PubMed 19352432
  8. Lehtiö L et al. (2008) Zinc binding catalytic domain of human tankyrase 1. J. Mol. Biol. 379, 136-145. PubMed 18436240