Neurotransmitter sodium symporter
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Sodium:neurotransmitter symporter family | |||||||||
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Identifiers | |||||||||
Symbol | SNF | ||||||||
TCDB | 2.A.22 | ||||||||
OPM superfamily | 64 | ||||||||
OPM protein | 2a65 | ||||||||
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A neurotransmitter sodium symporter (NSS) (TC# 2.A.22) is type of neurotransmitter transporter that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na+ symport mechanism.[1][2] The NSS family is a member of the APC superfamily. Its constituents have been found in bacteria, archaea and eukaryotes.
Function
Neurotransmitter transport systems are responsible for the release, re-uptake and recycling of
The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the
Neurotransmitter sodium symporters (NSS) are targets for anti-depressants, psychostimulants and other drugs.[4]
Transport reaction
The generalized transport reaction for the members of this family is:[2]
- solute (out) + Na+ (out) → solute (in) + Na+ (in).
Structure
The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine, taurine and other small molecules.[2]
NSS carriers are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport (see TC# 2.A.23). The latter couple glutamate and aspartate uptake to the cotransport of Na+ and the counter-transport of K+, with no apparent dependence on Cl−.[5] In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters.[6][7] Sequence analysis of the Na+/Cl− neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters.[8]
Tavoulari et al. (2011) described conversion of the Cl− -independent prokaryotic tryptophan transporter TnaT (2.A.22.4.1) to a fully functional Cl− -dependent form by a single point mutation, D268S. Mutations in TnaT-D268S, in wild type TnaT and in a serotonin transporter (SERT; 2.A.22.1.1) provided direct evidence for the involvement of each of the proposed residues in Cl− coordination. In both SERT and TnaT-D268S, Cl− and Na+ mutually increase each other's potency, consistent with am electrostatic interaction through adjacent binding sites.[9]
Crystal structures
There are several crystal structures available for a couple members of the NSS family:
- 2.A.22.1.7 - Dopamine transporter: 4M48, 4XP4, 4XP9, 4XPB, 4XPT
- 2.A.22.4.2 - The amino acid (leucine):2 Na+ symporter, LeuTAa: 2A65, 2Q6H, 2Q72, 2QB4, 2QJU, 3F3A, 3F3C, (more)
Subfamilies
Several characterized proteins are classified within the NSS family and can be found in the Transporter Classification Database.
Human proteins containing this domain
See also
- APC superfamily
- Membrane transport proteins
References
External links
- Transporter Classification Database (tcdb.org) for more detailed description of this family