Data from: Computational and experimental characterization of dVHL establish a Drosophila model of VHL syndrome

The von Hippel-Lindau (VHL) cancer syndrome is associated with mutations
in the VHL gene. The pVHL protein is involved in response to changes in
oxygen availability as part of an E3-ligase that targets the
Hypoxia-Inducible Factor for degradation. pVHL has a molten globule
configuration with marginal thermodynamic stability. The cancer-associated
mutations further destabilize it. The Drosophila homolog, dVHL, has
relatively low sequence similarity to pVHL, and is also involved in
regulating HIF1-α. Using in silico, in vitro and in vivo approaches we
demonstrate high similarity between the structure and function of dVHL and
pVHL. These proteins have a similar fold, secondary and tertiary
structures, as well as thermodynamic stability. Key functional residues in
dVHL are evolutionary conserved. This structural homology underlies
functional similarity of both proteins, evident by their ability to bind
their reciprocal partner proteins, and by the observation that transgenic
pVHL can fully maintain normal dVHL-HIF1-α downstream pathways in flies.
This novel transgenic Drosophila model is thus useful for studying the VHL
syndrome, and for testing drug candidates to treat it.