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Human NUDT16-like protein 1 (Syndesmos)

PDB Code 3KVH Target Class Nucleotide metabolism Target NUDT16L1 Alias MGC11275, NUDT16L1, SDOS Disease Area/Function cancer Date Deposited Nov 30 2009 Authors L.Trésaugues, M.I. Siponen, 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. Karlberg, T. Kotenyova, A. Kotzsch, P. Kraulis, M. Moche, T.K. Nielsen, T. Nyman, C. Persson, A.K. Roos, H. Schuler, P. Schutz, A.G. Thorsell, S. Van Den Berg, J. Weigelt, M. Welin, M. Wisniewska, P. Nordlund

About this structure

NUDT16L1 (Syndesmos) belongs to the NUDIX family of hydrolases. These proteins catalyze the hydrolysis of nucleoside diphosphates linked to a moiety, X [1]. Due to high sequence identity and conserved genetic organization, NUDT16L1 has been proposed to be the product of duplication of NUDT16 gene [2]. But striking differences exist between these two homologs: i) NUDT16 is nuclear [3] while NUDT16L1 is cytoplasmic [4], and ii) NUDT16 is a RNA decapping enzyme while NUDT16L1 has lost this ability but conserved RNA-binding properties [2]. Thus, the proposed role of NUDT16L1 is to serve as an intermediary in protein/RNA interactions occurring in the cytoplasm.

Here we have solved and refined to 1.7Ĺ the crystal structure of NUDT16L1 (PDB entry 3KVH) using the structure of NUDT16 (3COU) as a probe in molecular replacement trials. Overall structure and dimerization mode are conserved between NUDT16L1 and NUDT16.

Two points in this structure explain NUDT16L1 loss of catalytic activity. First, the NUDIX box, which is a conserved motif among the member of this family, is significantly altered in NUDT16L1. This motif has been shown to be critical in binding and positioning metals involved in phosphodiester bond hydrolysis. Then, a glutamate in NUDT16 present on the catalytic helix is replaced by a glycine in NUDT16L1. The structure of NUDT16L1 confirmed, then, that this residue was the catalytic base of NUDT16.

References

  1. Bessman, MJ, Frick, DN, and O'Handley, SF. The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes. J Biol Chem, 1996. 271(41): p. 25059-62. PubMed 8810257
  2. Taylor, MJ, and Peculis, BA. Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme. Nucleic Acids Res, 2008. 36(18): p. 6021-34. PubMed 18820299
  3. Ghosh, T, Peterson, B, Tomasevic, N, and Peculis, BA. Xenopus U8 snoRNA binding protein is a conserved nuclear decapping enzyme. Mol Cell, 2004. 13(6): p. 817-28. PubMed 15053875
  4. Baciu, PC, Saoncella, S, Lee, SH, Denhez, F, Leuthardt, D, and Goetinck, PF. Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization. J Cell Sci, 2000. 113 Pt 2: p. 315-24. PubMed 10633082