Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin

Nature Communications

Volumn 4, Issue , 2013, Pages

  Zebisch, Matthias ^a   Xu, Yang ^b,c   Krastev, Christos ^a   Macdonald, Bryan T ^b   Chen, Maorong ^b   Gilbert, Robert J C ^a   He, Xi ^b   Jones, E Yvonne ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

Author keywords

[No Author keywords available]

Indexed keywords

FRIZZLED PROTEIN; FURIN; FURIN 1; FURIN 2; MEMBRANE PROTEIN; R SPONDIN PROTEIN; RNF43 PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; WNT PROTEIN; ZNRF3 PROTEIN;

BIOPHYSICS; CHIMERA; EMBRYONIC DEVELOPMENT; ENZYME ACTIVITY; INHIBITION; MEMBRANE; MOLECULAR ANALYSIS; PROTEIN; VERTEBRATE;

ARTICLE; CELL ASSAY; CHIMERA; COMPLEX FORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIMERIZATION; ENZYME INHIBITION; MUTATION; NONHUMAN; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; WNT SIGNALING PATHWAY; XENOPUS; ZEBRA FISH;

VERTEBRATA;

ANIMALS; DIMERIZATION; DNA-BINDING PROTEINS; HUMANS; MICE; ONCOGENE PROTEINS; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED; THROMBOSPONDINS; UBIQUITIN-PROTEIN LIGASES; WNT SIGNALING PATHWAY; XENOPUS; ZEBRAFISH;

EID: 84889570757     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3787     Document Type: Article

References (48)

1. Kazanskaya, O. et al. R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev. Cell 7, 525-534 (2004 (Pubitemid 39341838)
2. Kim, K. A. et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309, 1256-1259 (2005
3. de Lau, W. B., Snel, B. & Clevers, H. C. The R-spondin protein family. Genome Biol. 13, 242 (2012
4. Parma, P. et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat. Genet. 38, 1304-1309 (2006 (Pubitemid 44646293)
5. Zhao, J. et al. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 132, 1331-1343 (2007 (Pubitemid 46627581)
6. Papapietro, O. et al. R-Spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea. Nat. Commun. 4, 1898 (2013
7. Seshagiri, S. et al. Recurrent R-spondin fusions in colon cancer. Nature 488, 660-664 (2012
8. Blaydon, D. C. et al. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. Nat. Genet. 38, 1245-1247 (2006 (Pubitemid 44646285)
9. Chishti, M. S., Kausar, N., Rafiq, M. A., Amin, M. & Ahmad, W. A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family. Br. J. Dermatol. 158, 621-623 (2008 (Pubitemid 351239165)
10. Khan, T. N. et al. Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1I).BMC Med. Genet. 13, 120 (2012
11. Carmon, K. S., Gong, X., Lin, Q., Thomas, A. & Liu, Q. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc. Natl Acad. Sci. USA 108, 11452-11457 (2011
12. Carmon, K. S., Lin, Q., Gong, X., Thomas, A. & Liu, Q. LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/beta-catenin signaling. Mol. Cell Biol. 32, 2054-2064 (2012
13. de Lau, W. et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476, 293-297 (2011
14. Glinka, A. et al. LGR4 and LGR5 are R-spondin receptors mediating Wnt/betacatenin and Wnt/PCP signalling. EMBO Rep. 12, 1055-1061 (2011
15. Ruffner, H. et al. R-Spondin potentiates Wnt/beta-catenin signaling through orphan receptors LGR4 and LGR5. PLoS One 7, e40976 (2012
16. Hao, H. X. et al. ZNRF3 promotes Wnt receptor turnover in an R-spondinsensitive manner. Nature 485, 195-200 (2012
17. Wu, J. et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc. Natl Acad. Sci. USA 108, 21188-21193 (2011
18. Koo, B. K. et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488, 665-669 (2012
19. Kim, K. A. et al. R-Spondin family members regulate the Wnt pathway by a common mechanism. Mol. Biol. Cell 19, 2588-2596 (2008
20. Nam, J. S., Turcotte, T. J., Smith, P. F., Choi, S. & Yoon, J. K. Mouse cristin/Rspondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J. Biol. Chem. 281, 13247-13257 (2006
21. Li, S. J. et al. Loss-of-function point mutations and two-furin domain derivatives provide insights about R-spondin2 structure and function. Cell Signal. 21, 916-925 (2009
22. Mahon, P. & Bateman, A. The PA domain: a protease-associated domain. Protein Sci. 9, 1930-1934 (2000
23. Anandasabapathy, N. et al. GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells. Immunity 18, 535-547 (2003 (Pubitemid 36513635)
24. Nurieva, R. I. et al. The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation. Immunity 32, 670-680 (2010
25. Chen, P. H., Chen, X., Lin, Z., Fang, D. & He, X. The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev. 27, 1345-1350 (2013
26. Peng, W. C. et al. Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. Cell Rep. 3, 1885-1892 (2013
27. Wang, D. et al. Structural basis for R-spondin recognition by LGR4/5/6 receptors. Genes Dev. 27, 1339-1344 (2013
28. Xu, K., Xu, Y., Rajashankar, K. R., Robev, D. & Nikolov, D. B. Crystal structures of Lgr4 and its complex with R-spondin1. Structure 21, 1683-1689 (2013
29. Deshaies, R. J. & Joazeiro, C. A. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78, 399-434 (2009
30. Plechanovova, A. et al. Mechanism of ubiquitylation by dimeric RING ligase RNF4. Nat. Struct. Mol. Biol. 18, 1052-1059 (2011
31. Aricescu, A. R., Lu, W. & Jones, E. Y. A time- and cost-efficient system for high-level protein production in mammalian cells. Acta Crystallogr. D Biol. Crystallogr. 62, 1243-1250 (2006 (Pubitemid 44526216)
32. Walter, T. S. et al. A procedure for setting up high-throughput nanolitre crystallization experiments. Crystallization workflow for initial screening, automated storage, imaging and optimization. Acta Crystallogr. D Biol. Crystallogr. 61, 651-657 (2005 (Pubitemid 43951502)
33. Vonrhein, C., Blanc, E., Roversi, P. & Bricogne, G. Automated structure solution with autoSHARP. Methods Mol. Biol. 364, 215-230 (2007 (Pubitemid 350183137)
34. Cowtan, K. The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr. D Biol. Crystallogr. 62, 1002-1011 (2006 (Pubitemid 44337374)
35. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D. Biol. Crystallogr. 60, 2126-2132 (2004 (Pubitemid 41742764)
36. Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-255 (1997 (Pubitemid 27235885)
37. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010
38. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007 (Pubitemid 47080256)
39. Davis, I. W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375-W383 (2007
40. Baker, N. A., Sept, D., Joseph, S., Holst, M. J. & McCammon, J. A. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl Acad. Sci. USA 98, 10037-10041 (2001 (Pubitemid 32802969)
41. Ashkenazy, H., Erez, E., Martz, E., Pupko, T. & Ben-Tal, N. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 38, W529-W533 (2010
42. Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007 (Pubitemid 47321791)
43. Schuck, P. Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. Biophys. J 78, 1606-1619 (2000 (Pubitemid 30141584)
44. Ortega, A., Amoros, D. & T. J., G. Prediction of hydrodynamic and other solution properties of rigid proteins from atomic- and residue-level models. Biophys. J. 101, 892-898 (2011
45. O'Callaghan, C. A. et al. BirA enzyme: production and application in the study of membrane receptor-ligand interactions by site-specific biotinylation. Anal. Biochem. 266, 9-15 (1999
46. Chen, S. et al. Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling. Dev. Cell 21, 848-861 (2011
47. Wei, Q. et al. R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J. Biol. Chem. 282, 15903-15911 (2007 (Pubitemid 47093310)
48. Ayadi, L. Molecular modelling of the TSR domain of R-spondin 4. Bioinformation 3, 119-123 (2008