Send to

Choose Destination
Sci Adv. 2018 May 11;4(5):eaar6179. doi: 10.1126/sciadv.aar6179. eCollection 2018 May.

Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.

Author information

Protein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen O, Denmark.
Department of Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark.
Molecular Modeling Group, Swiss Institute of Bioinformatics, Lausanne, Switzerland.


LeuT, a prokaryotic member of the neurotransmitter:sodium symporter (NSS) family, is an established structural model for mammalian NSS counterparts. We investigate the substrate translocation mechanism of LeuT by measuring the solution-phase structural dynamics of the transporter in distinct functional states by hydrogen/deuterium exchange mass spectrometry (HDX-MS). Our HDX-MS data pinpoint LeuT segments involved in substrate transport and reveal for the first time a comprehensive and detailed view of the dynamics associated with transition of the transporter between outward- and inward-facing configurations in a Na+- and K+-dependent manner. The results suggest that partial unwinding of transmembrane helices 1/5/6/7 drives LeuT from a substrate-bound, outward-facing occluded conformation toward an inward-facing open state. These hitherto unknown, large-scale conformational changes in functionally important transmembrane segments, observed for LeuT in detergent-solubilized form and when embedded in a native-like phospholipid bilayer, could be of physiological relevance for the translocation process.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center