ArticleProceedings of the National Academy of Sciences of the United States of America2013
Transient formation of water-conducting states in membrane transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed, 98 citations in OpenAlex.
- SLC Transporter-Mediated Functional Imaging in Cancer Diagnosis.Biomolecules · 2026Review
- An Orchestrated Interaction Network at the Binding Site of Human SERT Enables the Serotonin Occlusion and Import.Biochemistry · 2025Article
- Metabolic Energy is Stored in a Homeostatic Trans-Membrane Water Barochemical Gradient.The Journal of membrane biology · 2025Article
- 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
- SWEET family transporters act as water conducting carrier proteins in plants.bioRxiv : the preprint server for biology · 2024Article
- A Futile Cycle?: Tissue Homeostatic Trans-Membrane Water Co-Transport: Kinetics, Thermodynamics, Metabolic Consequences.bioRxiv : the preprint server for biology · 2024Article
- Review
- Cation Chloride Cotransporter NKCC1 Operates through a Rocking-Bundle Mechanism.Journal of the American Chemical Society · 2024Article
- Applications of Molecular Dynamics Simulations in Drug Discovery.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Influence of SGLT1 Sugar Uptake Inhibitors on Water Transport.Molecules (Basel, Switzerland) · 2023Article
- Collective Domain Motion Facilitates Water Transport in SGLT1.International journal of molecular sciences · 2023Article
- Insights into substrate transport and water permeation in the mycobacterial transporter MmpL3.Biophysical journal · 2023Article
- Pre-Training of Equivariant Graph Matching Networks with Conformation Flexibility for Drug Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1).ACS chemical neuroscience · 2022Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Molecular Dynamic Simulations and Molecular Docking as a Potential Way for Designed New Inhibitor Drug without Resistance.Tanaffos · 2022Review
- Modeling of SGLT1 in Reconstituted Systems Reveals Apparent Ion-Dependencies of Glucose Uptake and Strengthens the Notion of Water-Permeable Apo States.Frontiers in physiology · 2022Article
- Molecular mechanisms of brain water transport.Nature reviews. Neuroscience · 2021Review
- Characterization of the Features of Water Inside the SecY Translocon.The Journal of membrane biology · 2021Review
- Article
5 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
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Abstract
Membrane transporters rely on highly coordinated structural transitions between major conformational states for their function, to prevent simultaneous access of the substrate binding site to both sides of the membrane--a mode of operation known as the alternating access model. Although this mechanism successfully accounts for the efficient exchange of the primary substrate across the membrane, accruing evidence on significant water transport and even uncoupled ion transport mediated by transporters has challenged the concept of perfect mechanical coupling and coordination of the gating mechanism in transporters, which might be expected from the alternating access model. Here, we present a large set of extended equilibrium molecular dynamics simulations performed on several classes of membrane transporters in different conformational states, to test the presence of the phenomenon in diverse transporter classes and to investigate the underlying molecular mechanism of water transport through membrane transporters. The simulations reveal spontaneous formation of transient water-conducting (channel-like) states allowing passive water diffusion through the lumen of the transporters. These channel-like states are permeable to water but occluded to substrate, thereby not hindering the uphill transport of the primary substrate, i.e., the alternating access model remains applicable to the substrate. The rise of such water-conducting states during the large-scale structural transitions of the transporter protein is indicative of imperfections in the coordinated closing and opening motions of the cytoplasmic and extracellular gates. We propose that the observed water-conducting states likely represent a universal phenomenon in membrane transporters, which is consistent with their reliance on large-scale motion for function.
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