Structural basis of vilazodone dual binding mode to the serotonin transporter - Nature Communications

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 ...

nature.com

Faculty and academic positions – University of Copenhagen

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Squeeze pumping of lipids and insecticides by ABCH transporter

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.

cell.com

Trapping of spermine, Kukoamine A, and polyamine toxin blockers in GluK2 kainate receptor channels - Nature Communications

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,...

nature.com

A sodium channel mutant removes fast inactivation with the inactivation particle bound | Journal of General Physiology | Rockefeller University Press

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

rupress.org

Native DGC structure rationalizes muscular dystrophy-causing mutations - Nature

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

nature.com

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

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

nature.com

cell.com

Ion coupling and inhibitory mechanisms of the human presynaptic high-affinity choline transporter CHT1

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.

cell.com

Architecture of the high-affinity immunoglobulin E receptor

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

science.org

GABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway

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.

cell.com

Substrate translocation and inhibition in human dicarboxylate transporter NaDC3

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

rdcu.be

biorxiv.org

Insights into the distinct membrane targeting mechanisms of WDR91 family proteins

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.

cell.com

De novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder | The EMBO Journal

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 ...

embopress.org

Structure-guided design of a peripherally restricted chemogenetic system

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.

cell.com

Mechanism of ceramide synthase inhibition by fumonisin B1

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

sciencedirect.com

Molecular architecture of synaptic vesicles | PNAS

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

pnas.org

Membrane transporters modulating the toxicity of arsenic, cadmium, and mercury in human cells

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...

life-science-alliance.org

ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches

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...

mdpi.com

Structural basis for the reaction cycle and transport mechanism of human Na+-sulfate cotransporter NaS1 (SLC13A1)

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

science.org