The serotonin transporter (SERT) is a key antidepressant target. Here, authors present a cryo-EM structure where the antidepressant vilazodone spans the main SERT binding site toward a secondary ...

High-resolution cryo-EM structures and biochemical data reveal the dynamic process by which the ABCH transporter binds and transports lipid substrates and insecticides across cell membranes while detoxifying insecticides, providing atomic-level insights for the development of arthropod pest control agents and strategies for managing pesticide resistance.

Kainate receptors (KARs) contribute to excitatory neurotransmission, neuronal plasticity and neurological disorders. Here, Gangwar et al. present KAR structures in complex with channel blockers NpTx8,...

In this work, Liu and Bezanilla describe a voltage-gated sodium channel mutant that removes fast inactivation while the fast inactivation particle, the IFM

The detailed structure of the native dystrophin–glycoprotein complex provides mechanistic insights into mutations underlying muscular dystrophy.

Nature - Structure and mechanism of the Zorya anti-phage defense system

Qiu et al. report the cryo-EM structures of the human high-affinity choline transporter 1 (CHT1) with bound inhibitors, the substrate choline, and a substrate-free state. These structures reveal the binding modes of inhibitors with different chemical structures and shed light on the ion-coupled substrate transport mechanism of CHT1.

Structural analysis reveals species-specific differences in how the antibody IgE binds to its receptor FcεRI.

GABAA receptor π (GABRP) can form homopentameric channel-like structures, similar to the more common heteromeric type-A GABA receptor channels. However, GABRP activation by GABA uniquely induces a G-protein-signaling pathway rather than allowing chloride passage. Selective inhibition of GABRP signaling may hold therapeutic promise for GABRP-associated cancers.

Nature Structural & Molecular Biology - The authors show cryo-electron microscopy structures of the human high-affinity sodium–dicarboxylate cotransporter, responsible for dicarboxylate...

Proteins from the WDR91 family control phosphoinositide conversion required for endosome maturation. By combining structural, biochemical, and cellular data, Ma et al. provide evidence that two representative members of this family WDR91 and SORF1 either use the Rab7-binding WD40 domain or an amphipathic helix for membrane targeting.

imageimageVolume-regulated ion channels (VRACs) open in response to hypotonic stress and protect against excessive cell swelling and bursting. This study describes two patient variants in a VRAC subunit that cause a severe pleiotropic disorder ...

Kang et al. present HCAD, a peripherally restricted DREADD based on HCA2, with a chemical actuator that avoids crossing the blood-brain barrier and selectively reduces pain in mice. This system will enable the study of peripheral physiology without affecting the central nervous system.

Ceramide synthases (CerSs) play crucial roles in sphingolipid metabolism and have emerged as promising drug targets for metabolic diseases, cancers, a…

Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins ...

Non-essential metals are extremely toxic to living organisms, posing significant health risks, particularly in developing nations where they are a major contributor to illness and death. Although thei...

The ATP-binding cassette (ABC) and solute carrier (SLC) transporters play pivotal roles in cellular transport mechanisms, influencing a wide range of physiological processes and impacting various medi...

Five distinct conformations of human NaS1 provide insight into the mechanism of Na+-sulfate cotransport.

Here the authors determine a 2.8 Å cryo-EM structure of the Vo domain of V/A-ATPase, showing how protonation of Glu residues in the c12-ring drives ATP synthesis. Molecular dynamics simulations highli...

Cell Discovery - Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1

Five distinct conformations of human NaS1 provide insight into the mechanism of Na+-sulfate cotransport.