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Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters

2017    Gur, Mert; Cheng, Mary Hongying; Zomot, Elia; Bahar, Ivet

Dimerization is a common feature among the members of the neurotransmitter:sodium symporter (NSS) family of membrane proteins. Yet, the effect of dimerization on the mechanism of action of NSS members is not fully understood. In this study, we examined the collective dynamics of two members of the family, leucine transporter (LeuT) and dopamine transporter (DAT), to assess the significance of dimerization in modulating the functional motions of the monomers. We used to this aim the anisotropic network model (ANM), an efficient and robust method for modeling the intrinsic motions of proteins and their complexes. Transporters belonging to the NSS family are known to alternate between outward-facing (OF) and inward-facing (IF) states, which enable, the uptake and release of their substrate (neurotransmitter) respectively, as the substrate is transported: from the exterior to the interior of the cell. In both LeuT and DAT, dimerization is found to alter the collective motions intrinsically accessible to the individual monomers in favor of the functional transitions (OF IF), suggesting that dimerization may play a role in facilitating transport.