Residues in the eighth transmembrane domain of the proton-coupled folate transporter (SLC46A1) play an important role in defining the aqueous translocation pathway and in folate substrate binding.

ABSTRACT: The proton-coupled folate transporter (PCFT-SLC46A1) is required for intestinal folate absorption and folate transport across the choroid plexus. This report addresses the structure/function of the 8th transmembrane helix. Based upon biotinylation of cysteine-substituted residues by MTSEA-biotin, 14 contiguous exofacial residues to Leu316 were accessible to the extracellular compartment of the 23 residues in this helix (Leu303-Leu325). Pemetrexed blocked biotinylation of six Cys-substituted residues deep within the helix implicating an important role for this region in folate binding. Accessibility decreased at 4°C vs RT. The influx K_t, K_i and V_max were markedly increased for the P314C mutant, similar to what was observed for Y315A and Y315P mutants. Howeve

SUBMITTER: Aluri S 

PROVIDER: S-EPMC5624325 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature