Structure/function relationships within the VEGF/VEGF receptor families

The 8th International Duodecim symposium on "Endothelial growth factors in cancer and cardiovascular diseases" took place in the Vanajanlinna mansion from 9th to 11 June, 2011. It is just a bit more than 100 km from Helsinki and I did the trip by bicycle. This is the abstract for the poster I made for the meeting:

Structure/function relationships within the VEGF/VEGF receptor families

Leppänen, V-M.; Jeltsch, M.; Anisimov, A.; Tvorogov, D.; Aho, K.; Kalkkinen, N.; Toivanen, P.; Ylä-Herttuala, S.; Ballmer-Hofer, K.; Alitalo, K.

Members of the VEGF family of growth factors are central regulators of angiogenesis and lymphangiogenesis. There are many different VEGFs, but all bind to one or more VEGF receptors on the surface of mainly endothelial, but also a few other cell types. Every VEGF has a specific receptor binding pattern, which is mediated by the central VEGF homology domain (VHD). In additon to the VHD, most VEGFs contain one or two additional domains, which further differentiates their function.

While the first member of the VEGF family has been crystallized 15 years ago, the follow-up with structures from related growth factors was relatively slow. In addition, only one VEGF structure complexed with its receptor had been solved at the time. However, in the recent few years most of the VEGF family members have been crystallized, a few together with a corresponding VEGF receptor.

We have crystallized the VEGF-C/VEGFR-2(D2-3) complex and VEGF-D. We also analyzed receptor binding properties of several forms/mutants of the receptor and growth factor(s).
Our data provides deeper insight into the structural features that determine affinity and specificity within the VEGF/VEGFR system. While our understanding of the affinity- and specificity-determining elements has increased, we are still lacking some crucial parts be able to draw a complete picture, notably the structure of VEGFR-3.