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Molecular dynamics simulations of mitochondrial uncoupling protein 2
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SYSNO ASEP 0539523 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular dynamics simulations of mitochondrial uncoupling protein 2 Author(s) Škulj, S. (HR)
Brkljača, Z. (HR)
Kreiter, J. (AT)
Pohl, E. E. (AT)
Vazdar, Mario (UOCHB-X) ORCIDArticle number 1214 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 3 (2021)Number of pages 20 s. Language eng - English Country CH - Switzerland Keywords membrane protein ; long-chain fatty acid ; proton transfer ; purine nucleotide ; conductance measurements in model membranes ; uncoupling OECD category Physical chemistry Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 000615325400001 EID SCOPUS 85099936405 DOI 10.3390/ijms22031214 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2022 Electronic address https://doi.org/10.3390/ijms22031214
Number of the records: 1