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Can we explain differences in interactions of sFRPs with Wnt by in silico analysis?

Can we explain differences in interactions of sFRPs with Wnt by in silico analysis?. Catalina Hernàndez Sánchez Marlène Jagut Aline Stedman Karine Treguer Danuta Wawrzak. The canonical pathway Wnt 1,2,2b,3a,7a,7b,8,8b Fz 1,3, 5,7. The Ca2+ pathway Wnt 4,5a,11 Fz 2,7.

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Can we explain differences in interactions of sFRPs with Wnt by in silico analysis?

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  1. Can we explain differences in interactions of sFRPs with Wnt by in silico analysis? Catalina Hernàndez Sánchez Marlène Jagut Aline Stedman Karine Treguer Danuta Wawrzak

  2. The canonical pathway Wnt 1,2,2b,3a,7a,7b,8,8b Fz 1,3, 5,7 The Ca2+ pathway Wnt 4,5a,11 Fz 2,7 The Wnt binding partners The planar polarity pathway Wnt 5a,11 Fz 1,7

  3. The sFRPs structure CRD Cystein Rich Domain NTR Netrin domain • - Wnt binding domain. • CRD similar to the CRD of Fz • 10 conserved cysteines : 5 disulphide bridges. • Domain similar to the Netrins • Netrin = extracellular proteins • Netrin = control guidance of CNS commissuralaxons

  4. Differential interaction patterns of sFRPs with Wnts

  5. The sFRPs are highly conserved (ClustalW) X = xenopus G = chicken ZF = zebrafish M = mouse

  6. The sFRPs are highly conserved (ClustalW) X = xenopus G = chicken ZF = zebrafish M = mouse

  7. The sFRPs are highly conserved (ClustalW) sFRP1 and 5 are very close

  8. The sFRPs are highly conserved (ClustalW) X = xenopus G = chicken ZF = zebrafish M = mouse

  9. The sFRPs are highly conserved (ClustalW) X = xenopus G = chicken ZF = zebrafish M = mouse

  10. The sFRPs are highly conserved (ClustalW) X = xenopus G = chicken ZF = zebrafish M = mouse

  11. The sFRPs are highly conserved (ClustalW) sFRP4 and 3 are very close

  12. The CRD domain of sFRPs is highly conserved between the species (ClustalW) CRD of sFRP 3 CRD of sFRP 3 CRD of sFRP 3

  13. The CRD domain of sFRPs is highly conserved between the species (ClustalW) CRD of sFRP 3 CRD of sFRP 3 CRD of sFRP 3 10 cysteines residues

  14. Alignment of the five CRD domains of mouse sFRPs (ClustalW)

  15. Alignment of the five CRD domains of mouse sFRPs (ClustalW)

  16. Alignment of the five CRD domains of mouse sFRPs (ClustalW)

  17. Alignment of the five CRD domains of mouse sFRPs (ClustalW)

  18. PDB-blast to choose the good template to model sFRPs

  19. PDB-blast to choose the good template to model sFRPs PDB-blast for sFRP 1, 2 and 5: Template: CRD frizzled 8

  20. PDB-blast to choose the good template to model sFRPs PDB-blast for sFRP 1, 2 and 5: Template: CRD frizzled 8 PDB-blast for sFRP 3 and 4: Template: CRD sFRP3

  21. Modeling of the CRD domains sFRPs sFRP1 sFRP2 sFRP5 sFRP3 sFRP4 Template: CRD frizzled 8 Template: CRD sFRP3

  22. Comparison of the CRD domains of sFRP2 and sFRP4 sFRP2 sFRP4

  23. Comparison of the CRD domains of sFRP2 and sFRP4 sFRP2 sFRP4

  24. sFRP1 Merge sFRP1 and CRD sFRP3 Merge sFRP1 and Fz8 • Both of the templates give the same results (which is true for all the FRPs)

  25. sFRP4

  26. sFRP5

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