6xwm

Mechanism of substrate release in neurotransmitter:sodium symporters: the structure of LeuT in an inward-facing occluded conformation

spinqualitylabelsall models 6xwm, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xwm is a 2 chain structure with sequence from Aquifex aeolicus VF5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: NA, PHE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O67854_AQUAE Publication Abstract from PubMed Neurotransmitter:sodium symporters (NSS) are conserved from bacteria to man and serve as targets for drugs, including antidepressants and psychostimulants. Here we report the X-ray structure of the prokaryotic NSS member, LeuT, in a Na(+)/substrate-bound, inward-facing occluded conformation. To obtain this structure, we were guided by findings from single-molecule fluorescence spectroscopy and molecular dynamics simulations indicating that L-Phe binding and mutation of the conserved N-terminal Trp8 to Ala both promote an inward-facing state. Compared to the outward-facing occluded conformation, our structure reveals a major tilting of the cytoplasmic end of transmembrane segment (TM) 5, which, together with release of the N-terminus but without coupled movement of TM1, opens a wide cavity towards the second Na(+) binding site. The structure of this key intermediate in the LeuT transport cycle, in the context of other NSS structures, leads to the proposal of an intracellular release mechanism of substrate and ions in NSS proteins. X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release.,Gotfryd K, Boesen T, Mortensen JS, Khelashvili G, Quick M, Terry DS, Missel JW, LeVine MV, Gourdon P, Blanchard SC, Javitch JA, Weinstein H, Loland CJ, Nissen P, Gether U Nat Commun. 2020 Feb 21;11(1):1005. doi: 10.1038/s41467-020-14735-w. PMID:32081981 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Leucine transporter Symporter 3D structures

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