Structural characterisation of the CCN family growth factors (#305)
The CCN family growth factors are essential to a wide range of functional pathways in cellular signalling. They are heavily involved in development and disease, by mediating numbers of biological processes, including cell migration and chemotaxis, proliferation and survival, differentiation, angiogenesis, chondrogenesis and tumorigenesis. Several potential binding partners have been described in the literature so far (integrin, TGFbeta, Bone morphogenetic protein (BMP), Fibroblast growth factor receptor (FGFR), Notch, Wnt) yet little is known at the structural level of how CCN proteins interact with these proteins.
We are characterising the four functional domains of CCN proteins (insulin-like growth factor binding domain (IB), von Willebrand factor C domain (vWC), thrombospondin module 1 domain (TSP1), and C-terminal cystine-knot domain (CTCK)) structurally with an aim of elucidating their individual roles in different biological contexts. To this end, we present first crystal structures of vWC and TSP1 domains from CCN3 and discuss their features in comparison with other related proteins. CCN3 vWC domain can be subdivided into two subdomains similarly to Crossveinless2 vWC domain and Collagen IIA vWC domain. The structure CCN3 TSP1 domain aligns well and shares the fold of the CWR-layered core with that of thrombospondin-1 TSP1 domain. NMR study for the structure determination of CCN3 IB domain is in process. We will also present preliminary results of interaction analysis of CCN3 CTCK domain with various interactors.