| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, September 12, 1996, and in revised form, October 17, 1996)
From the Department of Microbiology, Groningen Biomolecular
Sciences and Biotechnology Institute, University of Groningen, Kerklaan
30, 9751 NN Haren, The Netherlands
Secondary glutamate transporters in neuronal and
glial cells in the mammalian central nervous system remove the
excitatory neurotransmitter glutamate from the synaptic cleft and
prevent the extracellular glutamate concentration to rise above
neurotoxic levels. Secondary structure prediction algorithms predict 6 transmembrane helices in the first half of the transporters but fail in
the C-terminal half where no clear helix-loop-helix motif is resolved in the hydropathy profile of the primary sequences. A number of previous studies have emphasized the importance of the C-terminal half
of the molecules for the function. Here we determine the membrane
topology of the C-terminal half of the glutamate transporters by
applying the phoA gene fusion technique to the homologous
bacterial glutamate transporter of Bacillus
stearothermophilus. High sequence conservation and very similar
hydropathy profiles in the C-terminal half warrant a similar folding as
in the glutamate transporters of the mammalian central nervous system.
The C-terminal half contains four putative transmembrane helices. The
strong hydrophobic moment and substitution moment of the most
C-terminal helix X that point to opposite faces of the helix suggest
that the helix faces the lipid environment with its least conserved,
hydrophobic face and the interior of the protein with its well
conserved, hydrophilic face. Residues that were shown before to be
critical for function cluster in helix X and VII.
Volume 271, Number 49,
Issue of December 6, 1996
pp. 31317-31321
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Huang and E. Tajkhorshid Dynamics of the Extracellular Gate and Ion-Substrate Coupling in the Glutamate Transporter Biophys. J., September 1, 2008; 95(5): 2292 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Koch and H. P. Larsson Small-Scale Molecular Motions Accomplish Glutamate Uptake in Human Glutamate Transporters J. Neurosci., February 16, 2005; 25(7): 1730 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Yurgel and M. L. Kahn Sinorhizobium meliloti dctA Mutants with Partial Ability To Transport Dicarboxylic Acids J. Bacteriol., February 1, 2005; 187(3): 1161 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Leighton, R. P. Seal, K. Shimamoto, and S. G. Amara A Hydrophobic Domain in Glutamate Transporters Forms an Extracellular Helix Associated with the Permeation Pathway for Substrates J. Biol. Chem., August 9, 2002; 277(33): 29847 - 29855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Eskandari, M. Kreman, M. P. Kavanaugh, E. M. Wright, and G. A. Zampighi Pentameric assembly of a neuronal glutamate transporter PNAS, July 18, 2000; 97(15): 8641 - 8646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grunewald and B. I. Kanner The Accessibility of a Novel Reentrant Loop of the Glutamate Transporter GLT-1 Is Restricted by Its Substrate J. Biol. Chem., March 24, 2000; 275(13): 9684 - 9689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Geest and J. S. Lolkema Membrane Topology and Insertion of Membrane Proteins: Search for Topogenic Signals Microbiol. Mol. Biol. Rev., March 1, 2000; 64(1): 13 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Slotboom, I. Sobczak, W. N. Konings, and J. S. Lolkema A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop PNAS, December 7, 1999; 96(25): 14282 - 14287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Masson, C. Sagne, M. Hamon, and S. E. Mestikawy Neurotransmitter Transporters in the Central Nervous System Pharmacol. Rev., September 1, 1999; 51(3): 439 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Slotboom, W. N. Konings, and J. S. Lolkema Structural Features of the Glutamate Transporter Family Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 293 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Eckhardt, B. Gotza, and R. Gerardy-Schahn Membrane Topology of the Mammalian CMP-Sialic Acid Transporter J. Biol. Chem., March 26, 1999; 274(13): 8779 - 8787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang and B. I. Kanner Two serine residues of the glutamate transporter GLT-1 are crucial for coupling the fluxes of sodium and the neurotransmitter PNAS, February 16, 1999; 96(4): 1710 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. PALACIN, R. ESTEVEZ, J. BERTRAN, and A. ZORZANO Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters Physiol Rev, October 1, 1998; 78(4): 969 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Mitrovic, S. G. Amara, G. A. R. Johnston, and R. J. Vandenberg Identification of Functional Domains of the Human Glutamate Transporters EAAT1 and EAAT2 J. Biol. Chem., June 12, 1998; 273(24): 14698 - 14706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zarbiv, M. Grunewald, M. P. Kavanaugh, and B. I. Kanner Cysteine Scanning of the Surroundings of an Alkali-Ion Binding Site of the Glutamate Transporter GLT-1 Reveals a Conformationally Sensitive Residue J. Biol. Chem., June 5, 1998; 273(23): 14231 - 14237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Slotboom, W. N. Konings, and J. S. Lolkema Cysteine-scanning Mutagenesis Reveals a Highly Amphipathic, Pore-lining Membrane-spanning Helix in the Glutamate Transporter GltT J. Biol. Chem., March 30, 2001; 276(14): 10775 - 10781. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
