Presentaci

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 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
sFRP4
sFRP2
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