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Article

Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2

1
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
2
Department of Biomedical Sciences, Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, 1210 Vienna, Austria
3
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 16610 Prague, Czech Republic
*
Authors to whom correspondence should be addressed.
Academic Editor: Masoud Jelokhani-Niaraki
Int. J. Mol. Sci. 2021, 22(3), 1214; https://doi.org/10.3390/ijms22031214
Received: 18 December 2020 / Revised: 19 January 2021 / Accepted: 22 January 2021 / Published: 26 January 2021
(This article belongs to the Special Issue Membrane Proteins: Structure, Function and Motion)
Molecular dynamics (MD) simulations of uncoupling proteins (UCP), a class of transmembrane proteins relevant for proton transport across inner mitochondrial membranes, represent a complicated task due to the lack of available structural data. In this work, we use a combination of homology modelling and subsequent microsecond molecular dynamics simulations of UCP2 in the DOPC phospholipid bilayer, starting from the structure of the mitochondrial ATP/ADP carrier (ANT) as a template. We show that this protocol leads to a structure that is impermeable to water, in contrast to MD simulations of UCP2 structures based on the experimental NMR structure. We also show that ATP binding in the UCP2 cavity is tight in the homology modelled structure of UCP2 in agreement with experimental observations. Finally, we corroborate our results with conductance measurements in model membranes, which further suggest that the UCP2 structure modeled from ANT protein possesses additional key functional elements, such as a fatty acid-binding site at the R60 region of the protein, directly related to the proton transport mechanism across inner mitochondrial membranes. View Full-Text
Keywords: membrane protein; long-chain fatty acid; proton transfer; purine nucleotide; conductance measurements in model membranes; uncoupling membrane protein; long-chain fatty acid; proton transfer; purine nucleotide; conductance measurements in model membranes; uncoupling
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MDPI and ACS Style

Škulj, S.; Brkljača, Z.; Kreiter, J.; Pohl, E.E.; Vazdar, M. Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2. Int. J. Mol. Sci. 2021, 22, 1214. https://doi.org/10.3390/ijms22031214

AMA Style

Škulj S, Brkljača Z, Kreiter J, Pohl EE, Vazdar M. Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2. International Journal of Molecular Sciences. 2021; 22(3):1214. https://doi.org/10.3390/ijms22031214

Chicago/Turabian Style

Škulj, Sanja, Zlatko Brkljača, Jürgen Kreiter, Elena E. Pohl, and Mario Vazdar. 2021. "Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2" International Journal of Molecular Sciences 22, no. 3: 1214. https://doi.org/10.3390/ijms22031214

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