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Nature. 2017 May 4;545(7652):66-70. doi: 10.1038/nature22057. Epub 2017 Apr 17.

Visualizing multistep elevator-like transitions of a nucleoside transporter.

Author information

1
Department of Biochemistry, Duke University Medical Center, 303 Research Drive, Durham, North Carolina 27710, USA.

Abstract

Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.

PMID:
28424521
PMCID:
PMC5567992
DOI:
10.1038/nature22057
[Indexed for MEDLINE]
Free PMC Article

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