CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

ABSTRACT: Na⁺-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na⁺-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number

SUBMITTER: Huynh KW 

PROVIDER: S-EPMC5834491 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature