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Amino Acids

, Volume 51, Issue 10–12, pp 1461–1474 | Cite as

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

  • Giovanni Minervini
  • Federica Quaglia
  • Francesco Tabaro
  • Silvio C. E. TosattoEmail author
Original Article
  • 148 Downloads

Abstract

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.

Keywords

Von Hippel–Lindau disease Hereditary neoplastic syndrome Cancer Bioinformatics 

Notes

Acknowledgements

The authors are grateful to the members of the BioComputingUP group for insightful discussions.

Funding

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.

Compliance with ethical standards

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.

Supplementary material

726_2019_2781_MOESM1_ESM.tiff (695 kb)
Figure S1. Ramachandran plot constructed for the VLP model using Procheck (TIFF 694 kb)
726_2019_2781_MOESM2_ESM.tiff (1.7 mb)
Figure S2. Analysis of 100 ns of MD simulation for VLP. Overall RMSD for the backbone heavy atoms calculated. RMSD value are expressed in Å, with each frame corresponding to 2 ps. The principal component analysis calculated for the entire simulation shows two main populations varying for N- and C-terminal tails orientations. The data is also confirmed by RMSF plotting of the two main representative structures. Cross-correlation analysis shows that these movements are not correlated (TIFF 1775 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Giovanni Minervini
    • 1
  • Federica Quaglia
    • 1
  • Francesco Tabaro
    • 1
    • 2
  • Silvio C. E. Tosatto
    • 1
    • 3
    Email author
  1. 1.Department of Biomedical SciencesUniversity of PadovaPaduaItaly
  2. 2.Institute of Biosciences and Medical TechnologyTampereFinland
  3. 3.CNR Institute of NeurosciencePaduaItaly

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