Identification of multiple substrate binding sites in SLC4 transporters in the outward-facing conformation: Insights into the transport mechanism
Hristina R. Zhekova, Alexander Pushkin, Gülru Kayık, Liyo Kao, Rustam Azimov, Natalia Abuladze, Debra Kurtz, Mirna Damergi, Sergei Y. Noskov, Ira Kurtz
Abstract
Solute carrier family 4 (SLC4) transporters mediate the transmembrane transport of HCO 3 -, CO 3 2-, and Cl -necessary for pH regulation, transepithelial H + /base transport, and ion homeostasis. Substrate transport with varying stoichiometry and specificity is achieved through an exchange mechanism and/or through coupling of the uptake of anionic substrates to typically co-transported Na + . Recently solved outward-facing structures of two SLC4 members (human anion exchanger 1 [hAE1] and human electrogenic sodium bicarbonate cotransporter 1 [hNBCe1]) with different transport modes (Cl -/HCO 3 -