ArticleNature2015
Transport domain unlocking sets the uptake rate of an aspartate transporter.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
What it found
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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.
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Who cites it
100 citing papers in PubMed, 164 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Automated kinetic-scheme-free sorting of single-molecule fluorescence events using a deep learning based hidden-state method.Nature communications · 2026Article
- Multimodal dynamics control activity of a glial glutamate transporter.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into cationic amino acid transport and viral receptor engagement by CAT1.Nature communications · 2025Article
- Advanced optical microscopy methods forBiophysical reviews · 2025Review
- Conformational free energy landscape of a glutamate transporter and microscopic details of its transport mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deep learning based local feature classification to automatically identify single molecule fluorescence events.Communications biology · 2024Article
- HS-AFM single-molecule structural biology uncovers basis of transporter wanderlust kinetics.Nature structural & molecular biology · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Review
- Structures and mechanisms of the Arabidopsis cytokinin transporter AZG1.Nature plants · 2024Article
- TRPV4 affects visual signals in photoreceptors and rod bipolar cells.Frontiers in cellular neuroscience · 2024Article
- Strategies for Overcoming the Single-Molecule Concentration Barrier.ACS measurement science au · 2023Review
- Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.Nature communications · 2023Article
- Discovery of (Journal of medicinal chemistry · 2022Article
- Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2.Nature communications · 2022Article
- The archaeal glutamate transporter homologue GltPh shows heterogeneous substrate binding.The Journal of general physiology · 2022Article
- Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1).ACS chemical neuroscience · 2022Article
- General principles of secondary active transporter function.Biophysics reviews · 2022Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Glutamate transporters terminate neurotransmission by clearing synaptically released glutamate from the extracellular space, allowing repeated rounds of signalling and preventing glutamate-mediated excitotoxicity. Crystallographic studies of a glutamate transporter homologue from the archaeon Pyrococcus horikoshii, GltPh, showed that distinct transport domains translocate substrates into the cytoplasm by moving across the membrane within a central trimerization scaffold. Here we report direct observations of these 'elevator-like' transport domain motions in the context of reconstituted proteoliposomes and physiological ion gradients using single-molecule fluorescence resonance energy transfer (smFRET) imaging. We show that GltPh bearing two mutations introduced to impart characteristics of the human transporter exhibits markedly increased transport domain dynamics, which parallels an increased rate of substrate transport, thereby establishing a direct temporal relationship between transport domain motion and substrate uptake. Crystallographic and computational investigations corroborated these findings by revealing that the 'humanizing' mutations favour structurally 'unlocked' intermediate states in the transport cycle exhibiting increased solvent occupancy at the interface between the transport domain and the trimeric scaffold.
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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.