Structural basis for the substrate recognition and transport mechanism of the human y⁺LAT1-4F2hc transporter complex.

ABSTRACT: Heteromeric amino acid transporters (HATs), including y⁺LAT1-4F2hc complex, are responsible for transporting amino acids across membranes, and mutations in y⁺LAT1 cause lysinuric protein intolerance (LPI), a hereditary disorder characterized by defective cationic amino acid transport. The relationship between LPI and specific mutations in y⁺LAT1 has yet to be fully understood. In this study, we characterized the function of y⁺LAT1-4F2hc complex in mammalian cells and determined the cryo-EM structures of the human y⁺LAT1-4F2hc complex in two distinct conformations: the apo state in an inward-open conformation and the native substrate-bound state in an outward-open conformation. Structural analysis suggests that Asp²⁴³ in y

SUBMITTER: Dai L 

PROVIDER: S-EPMC11922002 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature