Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloA computational study of ion current modulation in hVDAC3 induced by disulfide bonds
Anno di pubblicazione2016
Formato-
Autore/iGuardiani, Carlo; Leggio, Loredana; Scorciapino, Mariano Andrea; de Pinto, Vito; Ceccarelli, Matteo
Affiliazioni autoria Istituto Officina dei Materiali, Consiglio Nazionale delle Ricerche (CNR-IOM), UOS, Cagliari, Italy b Department of Biomedical and Biotechnological Sciences, BIOMETEC, University of Catania, Italy c National Institute for Biomembranes and Biosystems, Section of Catania, viale A. Doria 6, 95125 Catania, Italy d Department of Biomedical Sciences, Biochemistry Unit, University of Cagliari, Italy e Department of Physics, University of Cagliari, Cagliari, Italy
Autori CNR e affiliazioni
  • MATTEO CECCARELLI
Lingua/e
  • inglese
AbstractThe human VDAC channel exists in three isoforms characterized by high sequence homology and structural similarity. Yet the function and mode of action of hVDAC3 are still elusive. The presence of six surface cysteines exposed to the oxidizing environment of the mitochondrial inter-membrane space suggests the possible establishment of intramolecular disulfide bonds. Two natural candidates for disulfide bridge formation are Cys2 and Cys8 that, located on the flexible N-terminal domain, can easily come in contact. A third potentially important residue is Cys122 that is close to Cys2 in the homology model of VDAC3. Here we analyzed the impact of SS bonds through molecular dynamics simulations of derivatives of hVDAC3 (dubbed SS-2-8, SS-2-122, SS-8-122) including a single disulfide bond. Simulations showed that in SS-8-122, the fragment 1-7 crosses the top part of the barrel partially occluding the pore and causing a 20% drop of conductance. In order to identify other potential channel-occluding disulfide bonds, we used a set of neural networks and structural bioinformatics algorithms, after filtering with the steric constraints imposed by the 3D-structure. We identified other three species, namely SS-8-65, SS-2-36 and SS-8-36. While the conductance of SS-8-65 and SS-2-36 is about 30% lower than that of the species without disulfide bonds, the conductance of SS-8-36 was 40-50% lower. The results show how VDAC3 is able to modulate its pore size and current by exploiting the mobility of the N-terminal and forming, upon external stimuli, disulfide bridges with cysteine residues located on the barrel and exposed to the inter-membrane space. (C) 2016 Elsevier B.V. All rights reserved.
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Pagine da813
Pagine a823
Pagine totali11
RivistaBiochimica et biophysica acta. Biomembranes
Attiva dal 1967
Editore: Elsevier - Amsterdam
Paese di pubblicazione: Paesi Bassi
Lingua: inglese
ISSN: 0005-2736
Titolo chiave: Biochimica et biophysica acta. Biomembranes
Titolo proprio: Biochimica et biophysica acta.
Titolo abbreviato: Biochim. biophys. acta, Biomembr.
Titolo alternativo: BBA. Biomembranes
Numero volume della rivista1858
Fascicolo della rivista4
DOI10.1016/j.bbamem.2016.01.013
Verificato da refereeSì: Internazionale
Stato della pubblicazionePublished version
Indicizzazione (in banche dati controllate)
  • ISI Web of Science (WOS) (Codice:000372564500023)
Parole chiaveVoltage dependent anion channels, Cysteine oxidation states, Molecular dynamics, Structural bioinformatics, Neural networks, Conductance
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Strutture CNR
  • IOM — Istituto officina dei materiali
Moduli/Attività/Sottoprogetti CNR-
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