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

Giovanni Minervini; Federica Quaglia; Francesco Tabaro; Silvio C.E. Tosatto

doi:10.1007/s00726-019-02781-8

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

Giovanni Minervini
, Federica Quaglia
, Francesco Tabaro
, Silvio C.E. Tosatto^*

^*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

6 Sitaatiot (Scopus)

Abstrakti

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.

Alkuperäiskieli	Englanti
Sivut	1461-1474
Sivumäärä	14
Julkaisu	Amino Acids
Vuosikerta	51
Numero	10-12
DOI - pysyväislinkit	https://doi.org/10.1007/s00726-019-02781-8
Tila	Julkaistu - 2019
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

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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SDG 3 – Hyvä terveys ja hyvinvointi

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Jufo-taso 1

!!ASJC Scopus subject areas

Biochemistry
Clinical Biochemistry
Organic Chemistry

Pääsy asiakirjaan

10.1007/s00726-019-02781-8

Siteeraa tätä

@article{4d56d04ca863426890bcc69dade88a5d,

title = "Insights into the molecular features of the von Hippel–Lindau-like protein",

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 = "Bioinformatics, Cancer, Hereditary neoplastic syndrome, Von Hippel–Lindau disease",

author = "Giovanni Minervini and Federica Quaglia and Francesco Tabaro and Tosatto, \{Silvio C.E.\}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2019, Springer-Verlag GmbH Austria, part of Springer Nature. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

doi = "10.1007/s00726-019-02781-8",

language = "English",

volume = "51",

pages = "1461--1474",

journal = "Amino Acids",

issn = "0939-4451",

publisher = "Springer",

number = "10-12",

}

TY - JOUR

T1 - Insights into the molecular features of the von Hippel–Lindau-like protein

AU - Minervini, Giovanni

AU - Quaglia, Federica

AU - Tabaro, Francesco

AU - Tosatto, Silvio C.E.

N1 - Funding Information: 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. Publisher Copyright: © 2019, Springer-Verlag GmbH Austria, part of Springer Nature. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Bioinformatics

KW - Cancer

KW - Hereditary neoplastic syndrome

KW - Von Hippel–Lindau disease

U2 - 10.1007/s00726-019-02781-8

DO - 10.1007/s00726-019-02781-8

M3 - Article

C2 - 31485743

AN - SCOPUS:85072180336

SN - 0939-4451

VL - 51

SP - 1461

EP - 1474

JO - Amino Acids

JF - Amino Acids

IS - 10-12

ER -

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

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä