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?
Can we explain differences in
interactions of sFRPs with Wnt by in silico
analysis?Catalina Hernàndez Sánchez
Marlène JagutAline StedmanKarine Treguer
Danuta Wawrzak
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
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
Differential interaction patterns of sFRPs with
Wnts
X = xenopusG = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
X = xenopusG = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
sFRP1 and 5 are very close
The sFRPs are highly conserved (ClustalW)
X = xenopusG = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
X = xenopusG = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
X = xenopus G = chickenZF = zebrafishM = mouse
The sFRPs are highly conserved (ClustalW)
sFRP4 and 3 are very close
The sFRPs are highly conserved (ClustalW)
The CRD domain of sFRPs is highly conservedbetween the species (ClustalW)
CRD of sFRP 3
CRD of sFRP 3
CRD of sFRP 3
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
Alignment of the five CRD domains of mouse sFRPs (ClustalW)
Alignment of the five CRD domains of mouse sFRPs (ClustalW)
Alignment of the five CRD domains of mouse sFRPs (ClustalW)
Alignment of the five CRD domains of mouse sFRPs (ClustalW)
PDB-blast to choose the good template to model sFRPs
PDB-blast to choose the good template to model sFRPs
PDB-blast for sFRP 1, 2 and 5:
Template: CRD frizzled 8
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
Modeling of the CRD domains sFRPs
sFRP1 sFRP2 sFRP5 sFRP3 sFRP4
Template: CRD sFRP3Template: CRD frizzled 8
Comparison of the CRD domains of sFRP2 and sFRP4
sFRP4sFRP2
Comparison of the CRD domains of sFRP2 and sFRP4
sFRP2
sFRP4
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)
sFRP4
sFRP5