The dual-function glutamate transporters: structure and molecular characterisation of the substrate-binding sites.
Glutamate transporters are essential for terminating synaptic excitation and for maintaining extracellular glutamate concentrations below neurotoxic levels. These transporters also mediate a thermodynamically uncoupled chloride flux, activated by two of the molecules they transport, sodium and glutamate. Five eukaryotic glutamate transporters have been cloned and identified. They exhibit approximately 50% identity and this homology is even greater at the carboxyl terminal half, which is predicted to have an unusual topology. Determination of the topology shows that the carboxyl terminal part contains several transmembrane domains separated by two reentrant loops that are in close proximity to each other. We have identified several conserved amino acid residues in the carboxyl terminal half that play crucial roles in the interaction of the transporter with its substrates: sodium, potassium and glutamate. The conformation of the transporter gating the anion conductance is different from that during substrate translocation. However, there exists a dynamic equilibrium between these conformations.
Kanner
B I
BI
Department of Biochemistry, Hadassah Medical School, The Hebrew University, Jerusalem, Israel. kannerb@cc.huji.ac.il
Borre
L
L
D027322:Amino Acid Transport System X-AG / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002712:Chlorides / Q000737:chemistry; D003001:Cloning, Molecular; D027342:Excitatory Amino Acid Transporter 2 / Q000737:chemistry / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D002712:Chlorides; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; D001120:Arginine; D012964:Sodium