Mechanistic insights into mutation in the proton-coupled folate transporter (SLC46A1) causing hereditary folate malabsorption.

ABSTRACT: Hereditary folate malabsorption (HFM) is a rare, autosomal recessive disorder characterized by impaired intestinal absorption and impaired transport of folates across the choroid plexus into cerebral spinal fluid due to inactivating mutations in the human proton-coupled folate transporter (hPCFT) gene, which encodes the proton-coupled folate transporter (PCFT) SLC46A1. Understanding the structural impact of these mutations is crucial for elucidating the mechanistic basis for PCFT function and the pathophysiology of HFM. Recently, the cryo-electron microscopic structural characterization of the Gallus gallus PCFT was obtained, which shares significant sequence identity with hPCFT. We conducted molecular dynamics simulations of hPCFT based on this structure, to explore structural changes ind

SUBMITTER: Nandigrami P 

PROVIDER: S-EPMC11929075 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature