engleski

Molecular dynamics simulations of UCP2 protein – an insight to physiological function

Mitochondrial uncoupling protein 2 (UCP2) is a transmembrane protein localized in mitochondrial inner membrane working as a mitochondrial carrier. UCP2 belongs to a class of α-helical polytopic proteins and contains 309 residues. It is known that UCP2 protein is involved in maintaining proton gradient across cellular membranes with a help of fatty acids (FA). The mechanism how UCP2 protein and FA work together is still unknown.1 NMR structure of UCP2 protein was published in 20112, but according to recent results it has been shown that the extraction of UCP2 protein by detergents induces structural perturbations and distortions leading to physiologically irrelevant structure which has a large water channel connecting the two sides of a membrane.3 In order to get the physiologically relevant structure, we obtained and compared 1 s of MD simulations of two different structures – the published NMR structure and the homology modeled structure based on crystallographic structure of mitochondrial ADP/ATP carrier (ANT1) and primary UCP2 amino acid sequence. According to extensive MD simulations, the modeled structure appears to be more physiologically relevant than the NMR structure because it is more occluded and impervious to water as compared to the published NMR structure. The modeled UCP2 structure presents an excellent starting point for future MD simulations of functional properties of UCP2 protein in membranes.

molecular dynamics ; UCP2 protein ; ANT1 protein

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