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

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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

description

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. - PowerPoint PPT Presentation

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

Page 1: 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 JagutAline StedmanKarine Treguer

Danuta Wawrzak

Page 2: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

The Wnt binding partners

The canonical pathway

Wnt 1,2,2b,3a,7a,7b,8,8b

Fz 1,3, 5,7

The planar polarity pathway

Wnt 5a,11

Fz 1,7

The Ca2+ pathway

Wnt 4,5a,11

Fz 2,7

Page 3: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

The sFRPs structure

CRD Cystein Rich Domain

NTRNetrin 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

Page 4: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

Differential interaction patterns of sFRPs with

Wnts

Page 5: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

X = xenopusG = chickenZF = zebrafishM = mouse

The sFRPs are highly conserved (ClustalW)

Page 6: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

X = xenopusG = chickenZF = zebrafishM = mouse

The sFRPs are highly conserved (ClustalW)

Page 7: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

sFRP1 and 5 are very close

The sFRPs are highly conserved (ClustalW)

Page 8: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

X = xenopusG = chickenZF = zebrafishM = mouse

The sFRPs are highly conserved (ClustalW)

Page 9: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

X = xenopusG = chickenZF = zebrafishM = mouse

The sFRPs are highly conserved (ClustalW)

Page 10: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

X = xenopus G = chickenZF = zebrafishM = mouse

The sFRPs are highly conserved (ClustalW)

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sFRP4 and 3 are very close

The sFRPs are highly conserved (ClustalW)

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The CRD domain of sFRPs is highly conservedbetween the species (ClustalW)

CRD of sFRP 3

CRD of sFRP 3

CRD of sFRP 3

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10 cysteines residues

The CRD domain of sFRPs is highly conservedbetween the species (ClustalW)

CRD of sFRP 3

CRD of sFRP 3

CRD of sFRP 3

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

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

Page 16: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

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

Page 17: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

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

Page 18: Can we explain differences in interactions of sFRPs with Wnt by  in silico  analysis?

PDB-blast to choose the good template to model sFRPs

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PDB-blast to choose the good template to model sFRPs

PDB-blast for sFRP 1, 2 and 5:

Template: CRD frizzled 8

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PDB-blast to choose the good template to model sFRPs

PDB-blast for sFRP 1, 2 and 5:

PDB-blast for sFRP 3 and 4:

Template: CRD sFRP3

Template: CRD frizzled 8

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Modeling of the CRD domains sFRPs

sFRP1 sFRP2 sFRP5 sFRP3 sFRP4

Template: CRD sFRP3Template: CRD frizzled 8

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Comparison of the CRD domains of sFRP2 and sFRP4

sFRP4sFRP2

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Comparison of the CRD domains of sFRP2 and sFRP4

sFRP2

sFRP4

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sFRP1

Merge sFRP1 and Fz8 Merge sFRP1 and CRD sFRP3

Both of the templates give the same results (which is true for all the FRPs)

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sFRP4

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sFRP5