Ion and lipid orchestration of secondary active transport

• 成果类型: Review
• 署名作者: Drew, David; Boudker, Olga
• 署名单位: Stockholm University; Cornell University; Weill Cornell Medicine; Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6061
• DOI: 10.1038/s41586-024-07062-3
• 发表日期: 2024-02-29
• 页码: 963-974
• 关键词: crystal-structure; dopamine transporter; escherichia-coli; membrane-transport; bacterial homolog; conducting states; na+/h+ antiporter; lactose permease; binding-site; pot family

摘要

Transporting small molecules across cell membranes is an essential process in cell physiology. Many structurally diverse, secondary active transporters harness transmembrane electrochemical gradients of ions to power the uptake or efflux of nutrients, signalling molecules, drugs and other ions across cell membranes. Transporters reside in lipid bilayers on the interface between two aqueous compartments, where they are energized and regulated by symported, antiported and allosteric ions on both sides of the membrane and the membrane bilayer itself. Here we outline the mechanisms by which transporters couple ion and solute fluxes and discuss how structural and mechanistic variations enable them to meet specific physiological needs and adapt to environmental conditions. We then consider how general bilayer properties and specific lipid binding modulate transporter activity. Together, ion gradients and lipid properties ensure the effective transport, regulation and distribution of small molecules across cell membranes. This Review describes the various mechanisms of ion-coupled transport across membranes and how the activities of transporter proteins are modulated by the composition of the lipid bilayer.