ArticleProceedings of the National Academy of Sciences of the United States of America2016
Stochastic steps in secondary active sugar transport.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Metabolic Energy is Stored in a Homeostatic Trans-Membrane Water Barochemical Gradient.The Journal of membrane biology · 2025Article
- Molecular mechanisms and computational insights into human SGLTs: advancing toward selective SGLT1 inhibition.Frontiers in molecular biosciences · 2025Review
- A Futile Cycle?: Tissue Homeostatic Trans-Membrane Water Co-Transport: Kinetics, Thermodynamics, Metabolic Consequences.bioRxiv : the preprint server for biology · 2024Article
- Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.Nature communications · 2023Article
- Functional characterization of SGLT1 using SSM-based electrophysiology: Kinetics of sugar binding and translocation.Frontiers in physiology · 2023Article
- The sugar daddy: the role of the renal proximal tubule in glucose homeostasis.American journal of physiology. Cell physiology · 2022Review
- Equilibrium properties of E. coli lactose permease symport-A random-walk model approach.PloS one · 2022Article
- 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
- Function Trumps Form in Two Sugar Symporters,International journal of molecular sciences · 2021Review
- Active Glucose Transport 2020 and Beyond.Function (Oxford, England) · 2021Article
- Deciphering the Allosteric Process of theThe journal of physical chemistry. B · 2020Article
- A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms.PLoS computational biology · 2020Article
- A kinetic mechanism for enhanced selectivity of membrane transport.PLoS computational biology · 2020Article
- Computational Dissection of Membrane Transport at a Microscopic Level.Trends in biochemical sciences · 2020Review
- Molecular dynamics simulations of an engineered T4 lysozyme exclude helix to sheet transition, and provide insights into long distance, intra-protein switchable motion.Protein science : a publication of the Protein Society · 2020Article
- EmrE reminds us to expect the unexpected in membrane transport.The Journal of general physiology · 2020Article
- In silico characterization of residues essential for substrate binding of human cystine transporter, xCT.Journal of molecular modeling · 2019Article
- Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis.PLoS computational biology · 2019Article
- Inhibitor binding mode and allosteric regulation of NaNature communications · 2018Article
- Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.Diabetologia · 2018Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state.
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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.