Abstract
At synapses, sodium-coupled transporters remove released neurotransmitters, thereby recycling them and maintaining a low extracellular concentration of the neurotransmitter. The molecular mechanism underlying sodium-coupled neurotransmitter uptake is not completely understood. Several structures of homologs of human neurotransmitter transporters have been solved with X-ray crystallography. These crystal structures have spurred a plethora of computational and experimental work to elucidate the molecular mechanism underlying sodium-coupled transport. Here, we compare the structures of Glt Ph, a glutamate transporter homolog, and LeuT, a homolog of neurotransmitter transporters for the biogenic amines and inhibitory molecules GABA and glycine. We relate these structures to data obtained from experiments and computational simulations, to draw conclusions about the mechanism of uptake by sodium-coupled neurotransmitter transporters. Here, we propose how sodium and substrate binding is coupled and how binding of sodium and substrate opens and closes the gates in these transporters, thereby leading to an efficient coupled transport.
| Original language | English |
|---|---|
| Pages (from-to) | 694-705 |
| Number of pages | 12 |
| Journal | Structure |
| Volume | 21 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 7 2013 |
Fingerprint
ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Cite this
Neurotransmitter transporters : Structure meets function. / Focke, Paul J.; Wang, Xiaoyu; Larsson, Hans P.
In: Structure, Vol. 21, No. 5, 07.05.2013, p. 694-705.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neurotransmitter transporters
T2 - Structure meets function
AU - Focke, Paul J.
AU - Wang, Xiaoyu
AU - Larsson, Hans P
PY - 2013/5/7
Y1 - 2013/5/7
N2 - At synapses, sodium-coupled transporters remove released neurotransmitters, thereby recycling them and maintaining a low extracellular concentration of the neurotransmitter. The molecular mechanism underlying sodium-coupled neurotransmitter uptake is not completely understood. Several structures of homologs of human neurotransmitter transporters have been solved with X-ray crystallography. These crystal structures have spurred a plethora of computational and experimental work to elucidate the molecular mechanism underlying sodium-coupled transport. Here, we compare the structures of Glt Ph, a glutamate transporter homolog, and LeuT, a homolog of neurotransmitter transporters for the biogenic amines and inhibitory molecules GABA and glycine. We relate these structures to data obtained from experiments and computational simulations, to draw conclusions about the mechanism of uptake by sodium-coupled neurotransmitter transporters. Here, we propose how sodium and substrate binding is coupled and how binding of sodium and substrate opens and closes the gates in these transporters, thereby leading to an efficient coupled transport.
AB - At synapses, sodium-coupled transporters remove released neurotransmitters, thereby recycling them and maintaining a low extracellular concentration of the neurotransmitter. The molecular mechanism underlying sodium-coupled neurotransmitter uptake is not completely understood. Several structures of homologs of human neurotransmitter transporters have been solved with X-ray crystallography. These crystal structures have spurred a plethora of computational and experimental work to elucidate the molecular mechanism underlying sodium-coupled transport. Here, we compare the structures of Glt Ph, a glutamate transporter homolog, and LeuT, a homolog of neurotransmitter transporters for the biogenic amines and inhibitory molecules GABA and glycine. We relate these structures to data obtained from experiments and computational simulations, to draw conclusions about the mechanism of uptake by sodium-coupled neurotransmitter transporters. Here, we propose how sodium and substrate binding is coupled and how binding of sodium and substrate opens and closes the gates in these transporters, thereby leading to an efficient coupled transport.
UR - http://www.scopus.com/inward/record.url?scp=84877262325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877262325&partnerID=8YFLogxK
U2 - 10.1016/j.str.2013.03.002
DO - 10.1016/j.str.2013.03.002
M3 - Article
C2 - 23664361
AN - SCOPUS:84877262325
VL - 21
SP - 694
EP - 705
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 5
ER -