This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Slotboom, D. J.
Right arrow Articles by Lolkema, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Slotboom, D. J.
Right arrow Articles by Lolkema, J. S.

 Previous Article  |  Next Article 

Microbiology and Molecular Biology Reviews, June 1999, p. 293-307, Vol. 63, No. 2
1092-2172/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Structural Features of the Glutamate Transporter Family

Dirk Jan Slotboom, Wil N. Konings, and Juke S. Lolkema*

Department of Microbiology, Groningen Biotechnology and Molecular Sciences Institute, University of Groningen, 9751 NN Haren, The Netherlands

Neuronal and glial glutamate transporters remove the excitatory neurotransmitter glutamate from the synaptic cleft and thus prevent neurotoxicity. The proteins belong to a large and widespread family of secondary transporters, including bacterial glutamate, serine, and C4-dicarboxylate transporters; mammalian neutral-amino-acid transporters; and an increasing number of bacterial, archaeal, and eukaryotic proteins that have not yet been functionally characterized. Sixty members of the glutamate transporter family were found in the databases on the basis of sequence homology. The amino acid sequences of the carriers have diverged enormously. Homology between the members of the family is most apparent in a stretch of approximately 150 residues in the C-terminal part of the proteins. This region contains four reasonably well-conserved sequence motifs, all of which have been suggested to be part of the translocation pore or substrate binding site. Phylogenetic analysis of the C-terminal stretch revealed the presence of five subfamilies with characterized members: (i) the eukaryotic glutamate transporters, (ii) the bacterial glutamate transporters, (iii) the eukaryotic neutral-amino-acid transporters, (iv) the bacterial C4-dicarboxylate transporters, and (v) the bacterial serine transporters. A number of other subfamilies that do not contain characterized members have been defined. In contrast to their amino acid sequences, the hydropathy profiles of the members of the family are extremely well conserved. Analysis of the hydropathy profiles has suggested that the glutamate transporters have a global structure that is unique among secondary transporters. Experimentally, the unique structure of the transporters was recently confirmed by membrane topology studies. Although there is still controversy about part of the topology, the most likely model predicts the presence of eight membrane-spanning alpha -helices and a loop-pore structure which is unique among secondary transporters but may resemble loop-pores found in ion channels. A second distinctive structural feature is the presence of a highly amphipathic membrane-spanning helix that provides a hydrophilic path through the membrane. Recent data from analysis of site-directed mutants and studies on the mechanism and pharmacology of the transporters are discussed in relation to the structural model.

* Corresponding author. Mailing address: Biological Center, Department of Microbiology, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands. Phone: 31-50-3632155. Fax: 31-50-3632154. E-mail: j.s.lolkema{at}biol.rug.nl.

Microbiology and Molecular Biology Reviews, June 1999, p. 293-307, Vol. 63, No. 2
1092-2172/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ryan, R. M., Compton, E. L. R., Mindell, J. A. (2009). Functional Characterization of a Na+-dependent Aspartate Transporter from Pyrococcus horikoshii. J. Biol. Chem. 284: 17540-17548 [Abstract] [Full Text]  
  • White, J., Prell, J., James, E. K., Poole, P. (2007). Nutrient Sharing between Symbionts. Plant Physiol. 144: 604-614 [Full Text]  
  • Trainer, M. A., Yurgel, S. N., Kahn, M. L. (2007). Role of a Conserved Membrane Glycine Residue in a Dicarboxylate Transporter from Sinorhizobium meliloti. J. Bacteriol. 189: 2160-2163 [Abstract] [Full Text]  
  • Gendreau, S., Voswinkel, S., Torres-Salazar, D., Lang, N., Heidtmann, H., Detro-Dassen, S., Schmalzing, G., Hidalgo, P., Fahlke, C. (2004). A Trimeric Quaternary Structure Is Conserved in Bacterial and Human Glutamate Transporters. J. Biol. Chem. 279: 39505-39512 [Abstract] [Full Text]  
  • Burguiere, P., Auger, S., Hullo, M.-F., Danchin, A., Martin-Verstraete, I. (2004). Three Different Systems Participate in L-Cystine Uptake in Bacillus subtilis. J. Bacteriol. 186: 4875-4884 [Abstract] [Full Text]  
  • Sobczak, I., Lolkema, J. S. (2004). Alternating Access and a Pore-Loop Structure in the Na+-Citrate Transporter CitS of Klebsiella pneumoniae. J. Biol. Chem. 279: 31113-31120 [Abstract] [Full Text]  
  • Umesh, A., Cohen, B. N., Ross, L. S., Gill, S. S. (2003). Functional characterization of a glutamate/aspartate transporter from the mosquito Aedes aegypti. J. Exp. Biol. 206: 2241-2255 [Abstract] [Full Text]  
  • Marin, M., Lavillette, D., Kelly, S. M., Kabat, D. (2003). N-Linked Glycosylation and Sequence Changes in a Critical Negative Control Region of the ASCT1 and ASCT2 Neutral Amino Acid Transporters Determine Their Retroviral Receptor Functions. J. Virol. 77: 2936-2945 [Abstract] [Full Text]  
  • Arias, C. A., Pena, J., Panesso, D., Reynolds, P. (2003). Role of the transmembrane domain of the VanT serine racemase in resistance to vancomycin in Enterococcus gallinarum BM4174. J Antimicrob Chemother 51: 557-564 [Abstract] [Full Text]  
  • Wagenfeld, A., Yeung, C.-H., Lehnert, W., Nieschlag, E., Cooper, T. G. (2002). Lack of Glutamate Transporter EAAC1 in the Epididymis of Infertile c-ros Receptor Tyrosine-Kinase Deficient Mice. J Androl 23: 772-782 [Abstract] [Full Text]  
  • Seal, R. P., Shigeri, Y., Eliasof, S., Leighton, B. H., Amara, S. G. (2001). Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance. Proc. Natl. Acad. Sci. USA 98: 15324-15329 [Abstract] [Full Text]  
  • Krom, B. P., Aardema, R., Lolkema, J. S. (2001). Bacillus subtilis YxkJ Is a Secondary Transporter of the 2-Hydroxycarboxylate Transporter Family That Transports L-Malate and Citrate. J. Bacteriol. 183: 5862-5869 [Abstract] [Full Text]  
  • Dashper, S. G., Brownfield, L., Slakeski, N., Zilm, P. S., Rogers, A. H., Reynolds, E. C. (2001). Sodium Ion-Driven Serine/Threonine Transport in Porphyromonas gingivalis. J. Bacteriol. 183: 4142-4148 [Abstract] [Full Text]  
  • Marvin, J. S., Hellinga, H. W. (2001). Conversion of a maltose receptor into a zinc biosensor by computational design. Proc. Natl. Acad. Sci. USA 98: 4955-4960 [Abstract] [Full Text]  
  • Watzke, N., Rauen, T., Bamberg, E., Grewer, C. (2000). On the Mechanism of Proton Transport by the Neuronal Excitatory Amino Acid Carrier 1. JGP 116: 609-622 [Abstract] [Full Text]  
  • Marin, M., Tailor, C. S., Nouri, A., Kabat, D. (2000). Sodium-Dependent Neutral Amino Acid Transporter Type 1 Is an Auxiliary Receptor for Baboon Endogenous Retrovirus. J. Virol. 74: 8085-8093 [Abstract] [Full Text]  
  • Yurgel, S., Mortimer, M. W., Rogers, K. N., Kahn, M. L. (2000). New Substrates for the Dicarboxylate Transport System of Sinorhizobium meliloti. J. Bacteriol. 182: 4216-4221 [Abstract] [Full Text]  
  • Saier, M. H. Jr (2000). Families of transmembrane transporters selective for amino acids and their derivatives. Microbiology 146: 1775-1795 [Full Text]  
  • Eskandari, S., Kreman, M., Kavanaugh, M. P., Wright, E. M., Zampighi, G. A. (2000). Pentameric assembly of a neuronal glutamate transporter. Proc. Natl. Acad. Sci. USA 97: 8641-8646 [Abstract] [Full Text]  
  • Slotboom, D. J., Sobczak, I., Konings, W. N., Lolkema, J. S. (1999). A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop. Proc. Natl. Acad. Sci. USA 96: 14282-14287 [Abstract] [Full Text]  
  • Slotboom, D. J., Konings, W. N., Lolkema, J. S. (2001). Cysteine-scanning Mutagenesis Reveals a Highly Amphipathic, Pore-lining Membrane-spanning Helix in the Glutamate Transporter GltT. J. Biol. Chem. 276: 10775-10781 [Abstract] [Full Text]  
  • Tailor, C. S., Marin, M., Nouri, A., Kavanaugh, M. P., Kabat, D. (2001). Truncated Forms of the Dual Function Human ASCT2 Neutral Amino Acid Transporter/Retroviral Receptor Are Translationally Initiated at Multiple Alternative CUG and GUG Codons. J. Biol. Chem. 276: 27221-27230 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»