Insights into the molecular features of the von Hippel–Lindau-like protein
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We present an in silico characterization of the von Hippel–Lindau-like protein (VLP), the only known human paralog 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 simulations 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 understudied human protein. These may occur at precise hypoxia levels where functional overlap with pVHL may permit a finer modulation of pVHL functions.
KeywordsVon Hippel–Lindau disease Hereditary neoplastic syndrome Cancer Bioinformatics
The authors are grateful to the members of the BioComputingUP group for insightful discussions.
This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) Grant MFAG12740 and IG17753 to ST. FT is an AIRC research fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conflict of interest
The authors declare that they have no significant competing financial, professional or personal interests that might have influenced the performance or presentation of the work described in this manuscript.
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