Ca²⁺-mediated higher-order assembly of heterodimers in amino acid transport system b^0,+ biogenesis and cystinuria.

ABSTRACT: Cystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, causing recurrent kidney stones and kidney failure. Mutations of the regulatory glycoprotein rBAT and the amino acid transporter b^0,+AT, which constitute system b^0,+, are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Here, using electron cryo-microscopy and biochemistry, we discover that Ca²⁺ mediates higher-order assembly of system b^0,+. Ca²⁺ stabilizes the interface between two rBAT molecules, leading to super-dimerization of b^0,+AT-rBAT, which in turn facilitates N-glycan maturation and protein trafficking. A cystinu

SUBMITTER: Lee Y 

PROVIDER: S-EPMC9110406 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature