Cryo-EM structures reveal the H⁺/citrate symport mechanism of <i>Drosophila</i> INDY.

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 stabili

SUBMITTER: Kim S 

PROVIDER: S-EPMC11782487 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature