Minying Low

Abstract Mammalian organic solute transporter α/β (OSTα/β) is crucial for the enterohepatic circulation of bile acids and the homeostasis of steroid conjugates, mediating their movement across membranes as an obligate heterodimer. Here we present high-resolution cryo-EM structures of human OSTα/β in apo, substrate-bound and inhibitor-bound states, revealing a tetrameric organization as a homodimer of heterodimers that is required for membrane activity.

1 Introduction Proteins are the central executors of biological processes. A fundamental paradigm in modern protein biology is the recognition that proteins exist as conformational ensembles rather than a single “static” structure [1-3]. Nearly all protein-mediated processes, spanning enzyme catalysis, ligand binding, signal transduction to molecular transport, rely on transitions between conformational states, each displaying intra-state motions [4].