Structure and mechanism of a Na+-independent amino acid transporter

Paul L. Shaffer, April Goehring, Aruna Shankaranarayanan, Eric Gouaux

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1010-1014
Number of pages5
JournalScience
Volume325
Issue number5943
DOIs
StatePublished - 2009

Fingerprint

Amino Acid Transport Systems
Protons
Lysine
Amines
Sodium
Ions
Polyamines
Recycling
Cell Size
Leucine
Neurotransmitter Agents
Homeostasis
Amino Acids

ASJC Scopus subject areas

  • General

Cite this

Shaffer, P. L., Goehring, A., Shankaranarayanan, A., & Gouaux, E. (2009). Structure and mechanism of a Na+-independent amino acid transporter. Science, 325(5943), 1010-1014. https://doi.org/10.1126/science.1176088

Structure and mechanism of a Na+-independent amino acid transporter. / Shaffer, Paul L.; Goehring, April; Shankaranarayanan, Aruna; Gouaux, Eric.

In: Science, Vol. 325, No. 5943, 2009, p. 1010-1014.

Research output: Contribution to journalArticle

Shaffer, PL, Goehring, A, Shankaranarayanan, A & Gouaux, E 2009, 'Structure and mechanism of a Na+-independent amino acid transporter', Science, vol. 325, no. 5943, pp. 1010-1014. https://doi.org/10.1126/science.1176088
Shaffer, Paul L. ; Goehring, April ; Shankaranarayanan, Aruna ; Gouaux, Eric. / Structure and mechanism of a Na+-independent amino acid transporter. In: Science. 2009 ; Vol. 325, No. 5943. pp. 1010-1014.
@article{b74e79c2f8f24f0db14398992ef3e42c,
title = "Structure and mechanism of a Na+-independent amino acid transporter",
abstract = "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.",
author = "Shaffer, {Paul L.} and April Goehring and Aruna Shankaranarayanan and Eric Gouaux",
year = "2009",
doi = "10.1126/science.1176088",
language = "English (US)",
volume = "325",
pages = "1010--1014",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5943",

}

TY - JOUR

T1 - Structure and mechanism of a Na+-independent amino acid transporter

AU - Shaffer, Paul L.

AU - Goehring, April

AU - Shankaranarayanan, Aruna

AU - Gouaux, Eric

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=69249116947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249116947&partnerID=8YFLogxK

U2 - 10.1126/science.1176088

DO - 10.1126/science.1176088

M3 - Article

C2 - 19608859

AN - SCOPUS:69249116947

VL - 325

SP - 1010

EP - 1014

JO - Science

JF - Science

SN - 0036-8075

IS - 5943

ER -