ABSTRACT
Human EAAT1 and human EAAT2 are proteins of 542 amino acids and 574 amino acids, respectively. Hydropathy plotting indicates the presence of six amino-terminal transmembrane helices
followed by a large hydrophobic domain. The accessibility of residues in the large hydrophobic domain has been probed extensively in two studies to elucidate its secondary structure. Both studies developed similar topological models from these data. The study by Grunewald and Kanner13 proposes two reentry loops: one after transmembrane helix 6 and another after transmembrane helix 7. This array is followed by a helix, which runs in parallel to the membrane followed by transmembrane helix 8 and the cytosolic carboxy terminus. The study by Seal and Amara14 proposes only one reentrant loop after transmembrane helix 7 but two helices that lie parallel to the plane of the membrane before traversing it by helix 8 to form the cytosolic carboxy terminus. Substrate binding, Na+ binding, K+ binding, and H+ binding are thought to occur in this area.15 Glutamate transporters also display an anion conductance, which is thought to reside in the amino-terminal half of the protein.16
