J Mol Biol 2021 02 13;433(4):166764. Epub 2021 Jan 13.
Graduate Institute of Biochemistry, National Chung Hsing University, Taichung City 40227, Taiwan, ROC; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, 145 Xinda Rd., South Dist., Taichung City 40227, Taiwan, ROC; Ph.D. Program in Transnational Medicine, National Chung Hsing University, 145 Xinda Rd., South Dist., Taichung City 40227, Taiwan, ROC. Electronic address:
Apical sodium-dependent bile acid transporter (ASBT) catalyses uphill transport of bile acids using the electrochemical gradient of Na as the driving force. The crystal structures of two bacterial homologues ASBT and ASBT have previously been determined, with the former showing an inward-facing conformation, and the latter adopting an outward-facing conformation accomplished by the substitution of the critical Na-binding residue glutamate-254 with an alanine residue. While the two crystal structures suggested an elevator-like movement to afford alternating access to the substrate binding site, the mechanistic role of Na and substrate in the conformational isomerization remains unclear. Read More