We present an in silico characterization of the von Hippel-Lindau like protein (VLP), the only known human paralogue of the von Hippel-Lindau tumor suppressor protein (pVHL). Phylogenetic investigation showed VLP to be mostly conserved in upper mammals and specifically expressed in brain and testis. Structural analysis and molecular dynamics simulation show VLP to be very similar to pVHL three-dimensional organization and binding dynamics. In particular, conservation of elements at the protein interfaces suggests VLP to be a functional pVHL homolog potentially possessing multiple functions beyond HIF-1α-dependent binding activity. Our findings show that VLP may share at least seven interactors with pVHL, suggesting novel functional roles for this under- studied human protein. These may occur at precise hypoxia levels where functional overlap with pVHL may permit a finer modulation of pVHL functions.

Insights into the molecular features of the von Hippel-Lindau like protein