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Protein Sci
2008 Oct 01;1710:1761-70. doi: 10.1110/ps.036749.108.
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Helix XI contributes to the entrance of the serotonin transporter permeation pathway.
Torres-Altoro MI
,
White KJ
,
Rodríguez GJ
,
Nichols DE
,
Barker EL
.
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The sodium-dependent transporters for dopamine, norepinephrine, and serotonin that regulate neurotransmission, also translocate the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Previous studies implicated residues in transmembrane helix (TMH) XI of DAT as important sites for MPP(+) transport. We examined the importance of TMH XI residues F551 and F556 for MPP(+) translocation by human SERT. Mutations at hSERT F556, but not F551, reduced both 5-HT and MPP(+) transport compared to wild type. However, F556S/hSERT showed a reduction in surface expression explaining the decrease of transport activity for 5-HT, but did not account for the decrease in MPP(+) transport observed. Cysteine mutants at those positions confirmed the accessibility of hSERT/F556 to different methanethiosulfonate (MTS) reagents, suggesting its presence in a hydrophilic environment of the protein. In the presence of MTSET, current induced by 5-HT and MPP(+) was inhibited at the F556C mutant. In agreement with our homology model of SERT, based on the leucine transporter (LeuT(Aa)) from Aquifex aeolicus structure, these results are consistent with the hypothesis that a portion of TMH XI lines the entrance into the substrate permeation pathway.
Akabas,
Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
1992,
Pubmed
,
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Androutsellis-Theotokis,
A conformationally sensitive residue on the cytoplasmic surface of serotonin transporter.
2001,
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Beuming,
A comprehensive structure-based alignment of prokaryotic and eukaryotic neurotransmitter/Na+ symporters (NSS) aids in the use of the LeuT structure to probe NSS structure and function.
2006,
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Chen,
The third transmembrane domain of the serotonin transporter contains residues associated with substrate and cocaine binding.
1997,
Pubmed
Chen,
External cysteine residues in the serotonin transporter.
1997,
Pubmed
Chen,
Determination of external loop topology in the serotonin transporter by site-directed chemical labeling.
1998,
Pubmed
De Felice,
Serotonin and norepinephrine transporters: possible relationship between oligomeric structure and channel modes of conduction.
2001,
Pubmed
,
Xenbase
Gallardo-Godoy,
1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies.
2007,
Pubmed
Henry,
Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane domain I.
2003,
Pubmed
Humphreys,
Ligand binding to the serotonin transporter: equilibria, kinetics, and ion dependence.
1994,
Pubmed
Javitch,
Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.
1985,
Pubmed
Kamdar,
Functional role of critical stripe residues in transmembrane span 7 of the serotonin transporter. Effects of Na+, Li+, and methanethiosulfonate reagents.
2001,
Pubmed
Keller,
Cysteine-scanning mutagenesis of the fifth external loop of serotonin transporter.
2004,
Pubmed
Kitayama,
Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding.
1992,
Pubmed
Kitayama,
Dopamine transporter mutants selectively enhance MPP+ transport.
1993,
Pubmed
Martel,
Uptake of 1-methyl-4-phenylpyridinium (MPP+) by the JAR human placental choriocarcinoma cell line: comparison with 5-hydroxytryptamine.
2003,
Pubmed
Mitchell,
Structure and function of extracellular loop 4 of the serotonin transporter as revealed by cysteine-scanning mutagenesis.
2004,
Pubmed
Mitsuhata,
Tyrosine-533 of rat dopamine transporter: involvement in interactions with 1-methyl-4-phenylpyridinium and cocaine.
1998,
Pubmed
Ni,
A lithium-induced conformational change in serotonin transporter alters cocaine binding, ion conductance, and reactivity of Cys-109.
2001,
Pubmed
,
Xenbase
Paczkowski,
Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters.
1999,
Pubmed
Paczkowski,
Tyrosine residue 271 of the norepinephrine transporter is an important determinant of its pharmacology.
2001,
Pubmed
Ravna,
A homology model of SERT based on the LeuT(Aa) template.
2006,
Pubmed
Ravna,
A putative three-dimensional arrangement of the human serotonin transporter transmembrane helices: a tool to aid experimental studies.
2001,
Pubmed
Rodríguez,
Distinct recognition of substrates by the human and Drosophila serotonin transporters.
2003,
Pubmed
Sato,
Analysis of transmembrane domain 2 of rat serotonin transporter by cysteine scanning mutagenesis.
2004,
Pubmed
Sitte,
Quantitative analysis of inward and outward transport rates in cells stably expressing the cloned human serotonin transporter: inconsistencies with the hypothesis of facilitated exchange diffusion.
2001,
Pubmed
Sitte,
Characterization of carrier-mediated efflux in human embryonic kidney 293 cells stably expressing the rat serotonin transporter: a superfusion study.
2000,
Pubmed
White,
Engineered zinc-binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter.
2006,
Pubmed
Yamashita,
Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters.
2005,
Pubmed
