Structural basis for amino acid exchange by a human heteromeric amino acid transporter
Di Wu, Tamara N. Grund, Sonja Welsch, Deryck J. Mills, Max Michel, Schara Safarian, Hartmut Michel
Abstract
Significance Amino acids are involved in metabolism, protein biosynthesis, and signal transduction of humans. Heteromeric amino acid transporters maintain homeostasis of amino acid pools in various tissues and organs representing a unique group among members of the solute carrier superfamily. The neutral and basic amino acid transport complex (b [0,+] AT1-rBAT) is responsible for reabsorption of cystine and dibasic amino acids in kidney and intestine. Misguided trafficking, incomplete maturation, or defective transport activity result in hyperexcretion of cystine, causing cystinuria. While the function of this amino acid transport complex is known, details of its evolution, biogenesis, and mechanism of action have remained elusive. We determined the cryo-EM structure of this protein complex to gain a deeper understanding of its mode of action.