A home run for human NaCT/SLC13A5/INDY: cryo-EM structure and homology model to predict transport mechanisms, inhibitor interactions and mutational defects.

ABSTRACT: NaCT (SLC13A5) is a Na+-coupled transporter for citrate, which is expressed in the liver, brain, testes, and bone. It is the mammalian homolog of Drosophila INDY, a cation-independent transporter for citrate, whose partial loss extends lifespan in the organism. In humans, loss-of-function mutations in NaCT cause a disease with severe neurological dysfunction, characterized by neonatal epilepsy and delayed brain development. In contrast with humans, deletion of NaCT in mice results in a beneficial metabolic phenotype with protection against diet-induced obesity and metabolic syndrome; the brain dysfunction is not readily noticeable. The disease-causing mutations are located in different regions of human NaCT protein, suggesting that different mutations might have different mechanisms for th

SUBMITTER: Jaramillo-Martinez V 

PROVIDER: S-EPMC8203205 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature