A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport
| Autor: | Rachel A. Kolster, Matthias Quick, Harel Weinstein, Daniel S. Terry, Michael V. LeVine, Scott C. Blanchard, George Khelashvili, Jonathan A. Javitch, Zhou Zhou |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Multidisciplinary Synaptic cleft Chemistry Science Allosteric regulation General Physics and Astronomy Context (language use) General Chemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Förster resonance energy transfer Protein structure Symporter Biophysics lcsh:Q Binding site lcsh:Science 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Neurotransmitter:sodium symporters (NSS), targets of antidepressants and psychostimulants, clear neurotransmitters from the synaptic cleft through sodium (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the extracellular to intracellular space through an alternating access mechanism by coordinated conformational rearrangements in the symporter that alternately expose the binding sites to each side of the membrane. However, the mechanism by which the binding of ligands coordinates conformational changes occurring on opposite sides of the membrane is not well understood. Here, we report the use of single-molecule fluorescence resonance energy transfer (smFRET) techniques to image transitions between distinct conformational states on both the extracellular and intracellular sides of the prokaryotic NSS LeuT, including partially open intermediates associated with transport activity. The nature and functional context of these hitherto unidentified intermediate states shed new light on the allosteric mechanism that couples substrate and Na+ symport by the NSS family through conformational dynamics. |
| Databáze: | OpenAIRE |
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