Nature Communications (Feb 2020)
X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release
- Kamil Gotfryd,
- Thomas Boesen,
- Jonas S. Mortensen,
- George Khelashvili,
- Matthias Quick,
- Daniel S. Terry,
- Julie W. Missel,
- Michael V. LeVine,
- Pontus Gourdon,
- Scott C. Blanchard,
- Jonathan A. Javitch,
- Harel Weinstein,
- Claus J. Loland,
- Poul Nissen,
- Ulrik Gether
Affiliations
- Kamil Gotfryd
- Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen
- Thomas Boesen
- DANDRITE - Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University
- Jonas S. Mortensen
- Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen
- George Khelashvili
- Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University
- Matthias Quick
- Department of Psychiatry, Columbia University Vagelos College of Physicians & Surgeon and Division of Molecular Therapeutics, New York State Psychiatric Institute
- Daniel S. Terry
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Julie W. Missel
- Membrane Protein Structural Biology Group, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen
- Michael V. LeVine
- Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University
- Pontus Gourdon
- Membrane Protein Structural Biology Group, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen
- Scott C. Blanchard
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Jonathan A. Javitch
- Department of Psychiatry, Columbia University Vagelos College of Physicians & Surgeon and Division of Molecular Therapeutics, New York State Psychiatric Institute
- Harel Weinstein
- Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University
- Claus J. Loland
- Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen
- Poul Nissen
- DANDRITE - Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University
- Ulrik Gether
- Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen
- DOI
- https://doi.org/10.1038/s41467-020-14735-w
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
Neurotransmitter:sodium symporters (NSS) serve as targets for drugs including antidepressants and psychostimulants. Here authors report the X-ray structure of the prokaryotic NSS member, LeuT, in a Na+/substrate-bound, inward-facing occluded conformation which is a key intermediate in the LeuT transport cycle.
