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| Title | Cryo-EM structures reveal the H/citrate symport mechanism of INDY. |
|---|---|
| Journal, issue, pages | Life Sci Alliance, Vol. 8, Issue 4, Year 2025 |
| Publish date | Jan 30, 2025 |
Authors | Subin Kim / Jun Gyou Park / Seung Hun Choi / Ji Won Kim / Mi Sun Jin / ![]() |
| PubMed Abstract | 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 ... 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. |
External links | Life Sci Alliance / PubMed:39884835 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.7 - 3.65 Å |
| Structure data | EMDB-60210, PDB-8zkw: EMDB-60213, PDB-8zkz: EMDB-60215, PDB-8zl1: EMDB-60216, PDB-8zl2: EMDB-60217, PDB-8zl3: EMDB-60218, PDB-8zl4: EMDB-60220: Cryo-EM structure of the Drosophila INDY (apo inward-open, pH8) |
| Chemicals | ![]() ChemComp-PTY: ![]() ChemComp-NAG: ![]() ChemComp-4DS: ![]() ChemComp-FLC: |
| Source |
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Keywords | MEMBRANE PROTEIN / INDY / SLC13A5 / citrate transporter / DIDS / citrate |
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