ArticleProteins2015
Computational modeling of the N-terminus of the human dopamine transporter and its interaction with PIP2 -containing membranes.
Article in Proteins, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Multicolor Quantum Dot Tracking Uncovers Phenotypic Rescue of DAT A559V Aberrant Diffusion Upon D2R Antagonism.ACS chemical neuroscience · 2026Article
- Effects of the N-terminal dynamics on the conformational states of human dopamine transporter.Biophysical chemistry · 2022Article
- Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan.Frontiers in human neuroscience · 2022Review
- Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.Neuronal signaling · 2021Review
- Article
- SLC6 transporter oligomerization.Journal of neurochemistry · 2021Review
- The fine art of preparing membrane transport proteins for biomolecular simulations: Concepts and practical considerations.Methods (San Diego, Calif.) · 2021Review
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- The Role of Dopamine in the Stimulant Characteristics of Novel Psychoactive Substances (NPS)-Neurobiological and Computational Assessment Using the Case of Desoxypipradrol (2-DPMP).Frontiers in pharmacology · 2020Article
- Tales of tails in transporters.Open biology · 2019Review
- Structural Model of the ETR1 Ethylene Receptor Transmembrane Sensor Domain.Scientific reports · 2019Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Structure and Gating Dynamics of NaFrontiers in molecular biosciences · 2019Review
- The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties.BMC biology · 2018Article
- Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation.PloS one · 2018Article
- Phosphorylation of the Amino Terminus of the Dopamine Transporter: Regulatory Mechanisms and Implications for Amphetamine Action.Advances in pharmacology (San Diego, Calif.) · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The dopamine transporter (DAT) is a transmembrane protein belonging to the family of neurotransmitter:sodium symporters (NSS). Members of the NSS are responsible for the clearance of neurotransmitters from the synaptic cleft, and for their translocation back into the presynaptic nerve terminal. The DAT contains long intracellular N- and C-terminal domains that are strongly implicated in the transporter function. The N-terminus (N-term), in particular, regulates the reverse transport (efflux) of the substrate through DAT. Currently, the molecular mechanisms of the efflux remain elusive in large part due to lack of structural information on the N-terminal segment. Here we report a computational model of the N-term of the human DAT (hDAT), obtained through an ab initio structure prediction, in combination with extensive atomistic molecular dynamics (MD) simulations in the context of a lipid membrane. Our analysis reveals that whereas the N-term is a highly dynamic domain, it contains secondary structure elements that remain stable in the long MD trajectories of interactions with the bilayer (totaling >2.2 μs). Combining MD simulations with continuum mean-field modeling we found that the N-term engages with lipid membranes through electrostatic interactions with the charged lipids PIP2 (phosphatidylinositol 4,5-Biphosphate) or PS (phosphatidylserine) that are present in these bilayers. We identify specific motifs along the N-term implicated in such interactions and show that differential modes of N-term/membrane association result in differential positioning of the structured segments on the membrane surface. These results will inform future structure-based studies that will elucidate the mechanistic role of the N-term in DAT function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.