Sodium and Potassium e Channels and Pumps - Biological Inorganic Chemistry - page 189

Secondary active transporters, including EAATs, are thought to function through an alternating accessmechanism,
in which the substrate-binding site is alternatively accessible from the extracellular and intracellular sides through
a process that depends on one or more conformational changes. The determination of a number of crystal structures of
the archeal glutamate transporter orthologue Glt Ph from Pyrococcus horikoshii has enabled us to form a general
picture of howEAATs transport glutamate. Glt Ph exists as a trimer comprised of three identical subunits in the crystal.
Each protomer contains eight TMdomains and two re-entrant loops ( Figure 9.14 ). The first six TMdomains (TM1 e 6)

FIGURE 9.14 (D) Cartoon representation of the Glt Ph protomer viewed in the plane of the membrane. Transmembrane domain s1-6 coloured
in gray form a scaffold that holds the core translocation domain comprised of HP1 (yellow), TM7 (orange), HP2 (red), and TM8 (magenta).
Residue A307 in Glt Ph is shown as a blue sphere in the Glt Ph protomer (D). (E) View of a Glt Ph trimer parallel to the membrane. Subunits in the
trimer are coloured in green, magenta, or cyan. (From Jiang & Amara, 2011 . Reproduced with permission from Elsevier.)

form a scaffold surrounding a C-terminal core domain that contains structural elements required for the transport
mechanisms. This C-terminal translocation core domain includes two opposite-facing helical hairpins (HP1 andHP2),
which have been proposed to act as the inner and outer doors of the transporter, a seventh TM helix interrupted by