A5070435563- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Ion channel regulation and function
- Drug Transport and Resistance Mechanisms
- Chemical Synthesis and Analysis
- Neurobiology and Insect Physiology Research
- Amino Acid Enzymes and Metabolism
- Treatment of Major Depression
- Neural dynamics and brain function
- Protein Kinase Regulation and GTPase Signaling
- Advanced Fluorescence Microscopy Techniques
- Molecular Sensors and Ion Detection
- Protein Structure and Dynamics
- Tryptophan and brain disorders
- Parkinson's Disease Mechanisms and Treatments
- Hippo pathway signaling and YAP/TAZ
- Biochemical Analysis and Sensing Techniques
- Bipolar Disorder and Treatment
- Functional Brain Connectivity Studies
- Mental Health Research Topics
- Force Microscopy Techniques and Applications
University of Copenhagen
2016-2025
Maersk (Denmark)
2018-2025
Laboratory of Molecular Genetics
2020-2021
Université de Montréal
2021
Lundbeck Foundation
2010-2018
Foundation Center
2016-2017
Medical University of Vienna
2015
PharmacoGenetics (China)
2014
Stanford University
1995-2010
University of Wisconsin–Madison
2010
The movements of transmembrane segments (TMs) 3 and 6 at the cytoplasmic side membrane play an important role in activation G-protein-coupled receptors. Here we provide evidence for existence ionic lock that constrains relative mobility ends TM3 TM6 inactive state beta(2)-adrenergic receptor. We propose highly conserved Arg-131(3.50) end interacts both with adjacent Asp-130(3.49) Glu-268(6.30) TM6. Such a network interactions has now been directly supported by high-resolution structure...
Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. receptors can bind long C-terminal fragments NPY-e.g., NPY-(13-36)-peptide. In contrast, until now only characterized as NPY that do not such fragments. the present study an analog is presented, [Leu31, Pro34]NPY, which in a series human neuroblastoma cell lines on rat PC-12 cells displace radiolabeled from express those expressing The analog, [125I-Tyr36]...
G protein-coupled, seven-transmembrane segment receptors (GPCRs or 7TM receptors), with more than 1000 different members, comprise the largest superfamily of proteins in body. Since cloning first a decade ago, extensive experimental work has uncovered multiple aspects their function and challenged many traditional paradigms. However, it is only recently that we are beginning to gain insight into some most fundamental questions molecular this class receptors. How can, for example, so...
Mutations in several domains can lead to agonist-independent, constitutive activation of G protein-coupled receptors. However, the nature structural and molecular changes that constitutively turn on a receptor remains unknown. Here we show evidence activated mutant ²2 adrenergic (CAM) is characterized by instability an exaggerated conformational response ligand binding. The CAM could be demonstrated 4-fold increase rate denaturation purified at 37°C as compared with wild type receptor....
The purpose of the present study was to develop an approach directly monitor structural changes in a G protein-coupled receptor response drug binding. Purified human β2 adrenergic covalently labeled with cysteine-reactive, fluorescent probe N,N′-dimethyl-N-(iodoacetyl)-N′ - (7 nitrobenz -2 oxa -1,3diazol-4-yl)ethylenediamine (IANBD). IANBD is characterized by fluorescence which highly sensitive polarity its environment. We found that full agonist, isoproterenol, elicited stereoselective and...
Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson’s disease. Cell replacement therapies, particular embryonic stem (ES) cell-derived DA neurons, offer potential therapeutic venue for We sought to identify genes that can potentiate maturation ES cell cultures midbrain neuron phenotype. A number transcription factors have been implicated development by expression analyses loss-of-function knockout...
Movements of transmembrane segments (TMs) 3 and 6 play a key role in activation G protein-coupled receptors. However, the underlying molecular processes that govern these movements, accordingly control receptor activation, remain unclear. To elucidate importance conserved aspartic acid (Asp-130) Asp-Arg-Tyr motif β<sub>2</sub> adrenergic (β2AR), we mutated this residue to asparagine (D130N) mimic its protonated state, alanine (D130A) fully remove functionality side chain. Both mutants...
To validate the ICD-10 diagnosis of a single depressive episode as used in daily clinical psychiatric practice and recorded Danish Psychiatric Central Research Register.Patients discharged with were consecutively sampled from register diagnosed according to an interview using Schedules for Clinical Assessment Neuropsychiatry (SCAN).A total 75.4% 399 patients also got this SCAN (82.8% severe type depression, 76.0% moderate depression 65.2% mild depression).The can be sufficient precision. The...
Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort patients with atypical movement identified 2 DAT coding variants, DAT-Ile312Phe presumed de novo mutant DAT-Asp421Asn, in an adult male early-onset parkinsonism ADHD. According single-photon...
Non-traditional amphiphiles: Conferring aqueous solubility on membrane proteins generally requires the use of a detergent or other amphiphilic agent. A new class amphiphiles was synthesized, based steroidal lipophilic groups, and evaluated with several proteins. The results show that amphiphile, "glyco-diosgenin" (GDN; see figure), confers enhanced stability to variety in solution relative popular conventional detergents, such as dodecylmaltoside (DDM). Detailed facts importance specialist...