Structural Biology of Membrane Transporters: From Conformational Cycles to Therapeutic Modulation

Membrane transporters are essential for cellular homeostasis, controlling the movement of ions, metabolites, lipids, and xenobiotics across biological membranes. Two major transporter paradigms—secondary active transporters such as cation/proton antiporters (including Na+/H+ exchangers) and ATP-binding cassette (ABC) transporters—convert chemical energy into directional transport through coordinated conformational cycles. Despite major progress, key questions remain about how transporters couple energy input to substrate translocation, how selectivity is achieved, how dynamic transitions are regulated in native-like membranes, and how mutations or small molecules perturb these mechanisms in ways relevant to physiology and disease.This Research Topic aims to highlight advances in the structural biology of membrane transporters, emphasizing structure–function relationships, conformational landscapes, and experimentally validated mechanisms. We welcome contributions that capture distinct functional states, define ion/substrate binding and coupling principles, and reveal how lipids, pH, and interacting partners modulate transporter behavior. Studies bridging high-resolution structure determination with quantitative functional analysis are particularly encouraged, including work that leverages integrative approaches combining cryo-EM, cryo-ET, X-ray crystallography, NMR, computational modeling and simulations, and complementary biochemical and biophysical assays.A central goal of this Research Topic is to connect mechanistic insight across transporter families, linking shared design principles and distinct solutions evolved by ion-coupled and ATP-driven systems, while also encouraging translational perspectives. We welcome structure-guided studies of transporter pharmacology, clinically relevant variants, and strategies for modulating transporter activity. Methodological submissions are also encouraged, especially those addressing persistent challenges in membrane protein expression, stabilization, reconstitution, state trapping, validation, and reproducible workflows for studying transporter dynamics in native-like environments.Topics of interest include, but are not limited to:• Structural mechanisms of cation/proton antiporters and Na+/H+ exchange systems• Structural and mechanistic studies of ABC importers/exporters and their coupling to ATP hydrolysis• Conformational dynamics, intermediates, and alternating-access transitions• Ion/substrate selectivity, coupling stoichiometry, and allosteric regulation• Lipid dependence and membrane composition effects using native-like mimetics• Oligomerization, transient complexes, and regulatory partner interactions• State trapping with inhibitors, binders, mutations, or time-resolved strategies• Integrative pipelines linking structural states to transport kinetics and functional validation• Structure-guided discovery or optimization of transporter modulators and therapeutics• NMR-based atomic-level analysis of structure, dynamics, and conformational changes in membrane proteins. Topic editors: DR. MANISH DWIVEDI, Ruchika Bajaj Source: https://www.frontiersin.org/research-topics/78357/structural-biology-of-membrane-transporters-from-conformational-cycles-to-therapeutic-modulation