title: Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters.
abstract: 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 enables 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.
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Department of Mechanical Engineering, Istanbul Technical University (ITU) , Istanbul 34437, Turkey.
authors.forename: Mert
authors.identifier: 0000-0003-0983-4397
authors.initials: M
authors.lastname: Gur
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Mary Hongying
authors.initials: MH
authors.lastname: Cheng
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science , Rehovot 7610001, Israel.
authors.forename: Elia
authors.initials: E
authors.lastname: Zomot
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
mesh_terms: D016880:Anisotropy; D056004:Molecular Dynamics Simulation; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D027981:Symporters / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D027981:Symporters; D012964:Sodium