How Cryo-EM Has Expanded Our Understanding of Membrane Transporters

Abstract

Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to move diverse substrates across the membrane. However, the plasticity of these proteins’ ligand binding pockets, which allows them to bind a range of substrates, also poses a challenge for drug development. Here we highlight the structure, function, and transport mechanism of ATP-binding cassette/solute carrier transporters that are related to several diseases and multidrug resistance: ABCB1, ABCC1, ABCG2, SLC19A1, and SLC29A1. SIGNIFICANCE STATEMENT ATP-binding cassette transporters and solute carriers play vital roles in clinical chemotherapeutic outcomes. This paper describes the current understanding of the structure of five pharmacologically relevant transporters and how they interact with their ligands.

Cadmium transport by mammalian ATP-binding cassette transporters

“…The evolutionary-conserved ABC transporter superfamily is a large group of transmembrane (TM) transporters that utilize energy to translocate various substrates across membranes. Functional ABC transporters typically consist of at least two TM domains (TMDs) and two nucleotide binding domains (NBDs) (Ambudkar et al 2003 ), either synthesized from a single polypeptide chain for a full transporter or from two separate chains with each forming a half transporter harboring one TMD and NBD that come together to form a full transporter (Baril et al 2023 ; Alam and Locher 2023 ).…”