LAT1 (SLC7A5) catalyzes copper(histidinate) transport switching from antiport to uniport mechanism.

ABSTRACT: LAT1 (SLC7A5) is one of the most studied membrane transporters due to its relevance to physiology in supplying essential amino acids to brain and fetus, and to pathology being linked to nervous or embryo alterations; moreover, LAT1 over-expression is always associated with cancer development. Thus, LAT1 is exploited as a pro-drug vehicle and as a target for anti-cancer therapy. We here report the identification of a new substrate with pathophysiological implications, i.e., Cu-histidinate, and an unconventional uniport mechanism exploited for the Cu-histidinate transport. Crystals of the monomeric species Cu(His)₂ were obtained in our experimental conditions and the actual transport of the complex was evaluated by a combined strategy of bioinformatics, site-directed mutagenesis,

SUBMITTER: Scanga R 

PROVIDER: S-EPMC10492218 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature