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Crystal structures of LeuT reveal conformational dynamics in the outward-facing states.
Fan, Jianjun; Xiao, Yang; Quick, Matthias; Yang, Yuwei; Sun, Ziyi; Javitch, Jonathan A; Zhou, Xiaoming.
Afiliación
  • Fan J; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Xiao Y; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Quick M; Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University, New York, New York, USA; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
  • Yang Y; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Sun Z; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: ziyi.sun@scu.edu.cn.
  • Javitch JA; Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University, New York, New York, USA; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA; Department of Pharmacology, Vagelos College of Physicians and Su
  • Zhou X; Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: x.zhou@scu.edu.cn.
J Biol Chem ; 296: 100609, 2021.
Article en En | MEDLINE | ID: mdl-33811858
The neurotransmitter:sodium symporter (NSS) homolog LeuT from Aquifex aeolicus has proven to be a valuable model for studying the transport mechanism of the NSS family. Crystal structures have captured LeuT in key conformations visited during the transport cycle, allowing for the construction of a nearly complete model of transport, with much of the conformational dynamics studied by computational simulations. Here, we report crystal structures of LeuT representing new intermediate conformations between the outward-facing open and occluded states. These structures, combined with binding and accessibility studies, reveal details of conformational dynamics that can follow substrate binding at the central substrate binding site (S1) of LeuT in outward-facing states, suggesting a potential competition for direction between the outward-open and outward-occluded states at this stage during substrate transport. Our structures further support an intimate interplay between the protonation state of Glu290 and binding of Na1 that may ultimately regulate the outward-open-to-occluded transition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sodio / Proteínas Bacterianas / Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sodio / Proteínas Bacterianas / Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos