Structure and Mechanism of a Na+-Independent Amino Acid Transporter
Paul L. Shaffer,1
April Goehring,1
Aruna Shankaranarayanan,1
Eric Gouaux1,2
Amino acid, polyamine, and organocation (APC) transporters are
secondary transporters that play essential roles in nutrient
uptake, neurotransmitter recycling, ionic homeostasis, and regulation
of cell volume. Here, we present the crystal structure of apo-ApcT,
a proton-coupled broad-specificity amino acid transporter, at
2.35 angstrom resolution. The structure contains 12 transmembrane
helices, with the first 10 consisting of an inverted structural
repeat of 5 transmembrane helices like the leucine transporter
LeuT. The ApcT structure reveals an inward-facing, apo state
and an amine moiety of lysine-158 located in a position equivalent
to the sodium ion site Na2 of LeuT. We propose that lysine-158
is central to proton-coupled transport and that the amine group
serves the same functional role as the Na2 ion in LeuT, thus
demonstrating common principles among proton- and sodium-coupled
transporters.
2 Howard Hughes Medical Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
* To whom correspondence should be addressed. E-mail: gouauxe{at}ohsu.edu
