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Stochastic steps in secondary active sugar transport

Stochastic steps in secondary active sugar transport
Adelman, Joshua L.Ghezzi, ChiaraBisignano, PaolaLoo, Donald D. F.Choe, SeunghoAbramson, JeffRosenberg, John M.Wright, Ernest M.Grabe, Michael
DGIST Authors
Choe, Seungho
Issued Date
Article Type
WATER PERMEATIONActive TransportArticleControlled StudyCRYSTAL-STRUCTURECytoplasmembryoExtracellular SpaceFORCE-FIELDGalactoseGALACTOSE TRANSPORTERGLUCOSE COTRANSPORTERSHumanHuman CellIon TransportKineticsKineticsMarkov ChainMOLECULAR-DYNAMICS SIMULATIONSMolecular DynamicsNA+/GLUCOSE COTRANSPORTERPriority JournalProtein ConformationSGLTSIMULATIONSIMULATIONSodiumSodium Glucose Cotransporter 1Sodium IonSTATEStochastic ModelSubstrate ConcentrationSUBSTRATE RELEASESugarSugar TransportSymporterSymporterTransporterTransporter
Secondary active transporters, such as those that adopt the leucinetransporter 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.
National Academy of Sciences
Related Researcher
  • 최승호 Choe, Seungho 에너지공학과
  • Research Interests Theoretical Nuclear & Hadron Physics; Theoretical &Computational Biophysics
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School of Undergraduate Studies 1. Journal Articles


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