Subin Kim, Jun Gyou Park, Seung Hun Choi, Ji Won Kim, Mi Sun Jin
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引用次数: 0
Abstract
Drosophila I'm Not Dead Yet (INDY) functions as a transporter for citrate, a key metabolite in the citric acid cycle, across the plasma membrane. Partial deficiency of INDY extends lifespan, akin to the effects of caloric restriction. In this work, we use cryo-electron microscopy to determine structures of INDY in the presence and absence of citrate and in complex with the well-known inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) at resolutions ranging from 2.7 to 3.6 Å. Together with functional data obtained in vitro, the INDY structures reveal the H+/citrate co-transport mechanism, in which aromatic residue F119 serves as a one-gate element. They also provide insight into how protein-lipid interactions at the dimerization interface affect the stability and function of the transporter, and how DIDS disrupts the transport cycle.
期刊介绍：
Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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