Can we explain differences in interactions of sFRPs with Wnt by in silico analysis?
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Transcript of 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 JagutAline StedmanKarine Treguer
Danuta Wawrzak
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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
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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
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Differential interaction patterns of sFRPs with
Wnts
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X = xenopusG = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
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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?](https://reader035.fdocuments.us/reader035/viewer/2022081520/568159d1550346895dc721bd/html5/thumbnails/7.jpg)
sFRP1 and 5 are very close
The sFRPs are highly conserved (ClustalW)
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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?](https://reader035.fdocuments.us/reader035/viewer/2022081520/568159d1550346895dc721bd/html5/thumbnails/9.jpg)
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?](https://reader035.fdocuments.us/reader035/viewer/2022081520/568159d1550346895dc721bd/html5/thumbnails/10.jpg)
X = xenopus G = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
![Page 11: Can we explain differences in interactions of sFRPs with Wnt by in silico analysis?](https://reader035.fdocuments.us/reader035/viewer/2022081520/568159d1550346895dc721bd/html5/thumbnails/11.jpg)
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)
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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)
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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