The serotonin transporter (SERT), responsible for the reuptake of released serotonin, serves as a major target for antidepressants and psychostimulants. Nevertheless, refining the mechanistic models for SERT remains challenging. Here, we expand the molecular understanding of the binding of ions, substrates, and inhibitors to SERT by incorporating the fluorescent non-canonical amino acid Anap through genetic code expansion.
View Article and Find Full Text PDFThe neurotransmitter:sodium symporters (NSSs) are secondary active transporters that couple the reuptake of substrate to the symport of one or two sodium ions. One bound Na (Na1) contributes to the substrate binding, while the other Na (Na2) is thought to be involved in the conformational transition of the NSS. Two NSS members, the serotonin transporter (SERT) and the dopamine transporter (dDAT), also couple substrate uptake to the antiport of K by a largely undefined mechanism.
View Article and Find Full Text PDFMembrane protein structures are essential for the molecular understanding of diverse cellular processes and drug discovery. Detergents are not only widely used to extract membrane proteins from membranes but also utilized to preserve native protein structures in aqueous solution. However, micelles formed by conventional detergents are suboptimal for membrane protein stabilization, necessitating the development of novel amphiphilic molecules with enhanced protein stabilization efficacy.
View Article and Find Full Text PDFIn this paper, we examine ethnic discrimination using sport as a laboratory. Applying a field experiment in the three Scandinavian countries-Sweden, Norway, and Denmark-we test whether foreign female minority groups experience greater rejection rates when seeking inclusion in amateur soccer clubs. Soccer coaches were contacted by e-mail using native and foreign-sounding names from selected groups, requesting to participate in trial practice.
View Article and Find Full Text PDFMembrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to solubilize, stabilize, and crystallize membrane proteins, but membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation. Thus, developing novel detergents with enhanced efficacy for protein stabilization remains important.
View Article and Find Full Text PDFMembrane protein structures provide atomic level insight into essential biochemical processes and facilitate protein structure-based drug design. However, the inherent instability of these bio-macromolecules outside lipid bilayers hampers their structural and functional study. Detergent micelles can be used to solubilize and stabilize these membrane-inserted proteins in aqueous solution, thereby enabling their downstream characterizations.
View Article and Find Full Text PDFMembrane proteins are widely studied in detergent micelles, a membrane-mimetic system formed by amphiphilic compounds. However, classical detergents have serious limitations in their utility, particularly for unstable proteins such as eukaryotic membrane proteins and membrane protein complexes, and thus, there is an unmet need for novel amphiphiles with enhanced ability to stabilize membrane proteins. Here, we developed a new class of malonate-derived detergents with four glucosides, designated malonate-derived tetra-glucosides (MTGs), and compared these new detergents with previously reported octyl glucose neopentyl glycol (OGNG) and -dodecyl-β-d-maltoside (DDM).
View Article and Find Full Text PDFBackground: It is a policy objective to increase the percentage of journeys made by bicycle in Norway from the current 5 % to 10 %. Kristiansand is one of the most active cities in Norway in terms of cycling. We wished to identify the extent of injuries among cyclists admitted to the hospital.
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