Xinzhe Yu, Guanghui Yang, Chuangye Yan, Javier L Baylon, Jing Jiang, He Fan,
Guifeng Lu, Kazuya Hasegawa, Hideo Okumura, Tingliang Wang, Emad Tajkhorshid,
Shuo Li, and Nieng Yan.
Dimeric structure of the uracil: proton symporter UraA provides
mechanistic insights into the SLC4/23/26 transporters.
Cell Research, 27:1020-1033, 2017.
(PMC: PMC5539350)
YU2017-ET
The Escherichia coli uracil:proton symporter UraA is a prototypical member of
the nucleobase/ascorbate transporter (NAT) or nucleobase/cation symporter 2
(NCS2) family, which corresponds to the human solute carrier family SLC23.
UraA consists of 14 transmembrane segments (TMs) that are organized into
two distinct domains, the core domain and the gate domain, a structural fold
that is also shared by the SLC4 and SLC26 transporters. Here we present the
crystal structure of UraA bound to uracil in an occluded state at 2.5 Å
resolution. Structural comparison with the previously reported inward-open
UraA reveals pronounced relative motions between the core domain and the
gate domain as well as intra-domain rearrangement of the gate domain. The
occluded UraA forms a dimer in the structure wherein the gate domains are
sandwiched by two core domains. In vitro and in vivo biochemical
characterizations show that UraA is at equilibrium between dimer and
monomer in all tested detergent micelles, while dimer formation is necessary
for the transport activity. Structural comparison between the dimeric UraA and
the recently reported inward-facing dimeric UapA provides important insight
into the transport mechanism of SLC23 transporters.
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