A computational study of ion current modulation in hVDAC3 induced by disulfide bonds

Biochimica Et Biophysica Acta
Carlo GuardianiMatteo Ceccarelli

Abstract

The 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. Whil...Continue Reading

References

Sep 15, 1973·Journal of Molecular Biology·A Shrake, J A Rupley
Dec 1, 1996·Journal of Molecular Graphics·O S SmartM S Sansom
Apr 26, 2003·Trends in Biochemical Sciences·Philip J Hogg
Jun 28, 2005·Nucleic Acids Research·F Ferrè, P Clote
Aug 13, 2005·The Journal of Chemical Physics·Gabriele PetraglioMichele Parrinello
Apr 4, 2006·Cardiovascular Research·Aleksey V Zima, Lothar A Blatter
Jul 18, 2006·Nucleic Acids Research·Alessio CeroniPaolo Frasconi
Nov 23, 2006·Biophysical Journal·Marcos SotomayorKlaus Schulten
Mar 3, 2007·BMC Evolutionary Biology·Matthew J YoungDeborah A Court
Feb 22, 2008·Protein Science : a Publication of the Protein Society·Ricardo SanchezJamil Momand
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Monika BayrhuberKornelius Zeth
Nov 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Rachna UjwalJeff Abramson
Jun 17, 2009·Biophysical Journal·Christopher Maffeo, Aleksei Aksimentiev
Oct 7, 2009·Biophysical Journal·Soroosh PezeshkiUlrich Kleinekathöfer
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Morten Ø JensenDavid E Shaw
Mar 30, 2010·Molecular Aspects of Medicine·Varda Shoshan-BarmatzNir Arbel
Apr 22, 2010·Proteins·Kresten Lindorff-LarsenDavid E Shaw
Feb 2, 2011·Biophysical Journal·Huan RuiWonpil Im
Feb 23, 2011·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Amit KumarMatteo Ceccarelli
Oct 18, 2011·Biochimica Et Biophysica Acta·James GumbartBenoît Roux
Oct 25, 2011·Biochimica Et Biophysica Acta·Angela MessinaVito De Pinto
Dec 14, 2011·The Journal of Biological Chemistry·Stefano M Marino, Vadim N Gladyshev
Jan 14, 2012·Biochimica Et Biophysica Acta·Marco Colombini
Dec 1, 2012·Nanoscale·Niraj ModiUlrich Kleinekathöfer
Jul 19, 2013·The Journal of Biological Chemistry·Claudia M Cremers, Ursula Jakob
Jul 23, 2013·The Journal of Biological Chemistry·Svetlana Rajkumar Maurya, Radhakrishnan Mahalakshmi

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Citations

Mar 8, 2016·Biochimica Et Biophysica Acta·Vito De PintoRadhakrishnan Mahalakshmi
Jan 25, 2019·The Journal of General Physiology·Ankit Gupta, Radhakrishnan Mahalakshmi
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Simona ReinaRosaria Saletti
Jan 10, 2017·Frontiers in Oncology·Simona ReinaVito De Pinto
Sep 20, 2020·Biomolecules·Loredana LeggioNunzio Iraci
Sep 11, 2021·ACS Chemical Neuroscience·Altmash KhanRadhakrishnan Mahalakshmi

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