A5022643930- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Signaling Pathways in Disease
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Photoreceptor and optogenetics research
- Protein purification and stability
- Neural dynamics and brain function
- Semiconductor materials and devices
- Computational Drug Discovery Methods
- Toxin Mechanisms and Immunotoxins
Weill Cornell Medicine
2022-2024
Cornell University
2021-2024
National Institutes of Health
2023-2024
National Institute of Neurological Disorders and Stroke
2024
Abstract The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made a target for therapeutic immunomodulation to block its activity suppress cell activation. Here, we report structures of human alone, with nanobody inhibitor, an antibody-toxin fusion blocker. Rather than directly, four copies bind tetramer’s voltage sensing domains pore domain induce inactive conformation. In contrast, docks toxin at extracellular...
The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane (TMDs) drive intracellular signaling. Pharmacologically, mGluRs can be targeted at the LBDs by synthetic orthosteric compounds or TMDs allosteric modulators. Despite potential of therapeutics, an understanding functional structural basis their effects is limited. Here we use multiple...
The kainate receptors (KARs) are members of the ionotropic glutamate receptor family and assemble into tetramers from a pool five subunit types (GluK1-5). Each confers distinct functional properties to receptor, but compositional stoichiometric diversity KAR is not well understood. To address this, we first solve structure GluK1 homomer, which enables systematic assessment structural compatibility among subunits. Next, analyze single-cell RNA sequencing data, reveal extreme in combinations...
Abstract The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane (TMDs) drive intracellular signaling. Pharmacologically, mGluRs can be targeted either at the LBDs by synthetic orthosteric compounds or TMDs allosteric modulators. Despite potential of TMD-targeting therapeutics, an understanding functional structural basis their effects on is...
ABSTRACT The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made a target for therapeutic immunomodulation to block its activity suppress cell activation. We determined structures of human alone, with nanobody inhibitor, an antibody-toxin fusion blocker. Rather than directly, four copies bind tetramer’s voltage sensing domains pore domain induce inactive conformation. In contrast, docks toxin at extracellular...