Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT: Recommended in F1000Prime as being of special significance in its field by F1000 Faculty Member Robert Vandenberg
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- Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT
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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.
Originalsprog | Engelsk |
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Artikelnummer | eaar6179 |
Tidsskrift | Science Advances |
Vol/bind | 4 |
Udgave nummer | 5 |
Antal sider | 12 |
ISSN | 2375-2548 |
DOI | |
Status | Udgivet - 2018 |
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