A5016127718- Advanced Electron Microscopy Techniques and Applications
- Electron and X-Ray Spectroscopy Techniques
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Advanced X-ray Imaging Techniques
- Photosynthetic Processes and Mechanisms
- Ion channel regulation and function
- Neuropeptides and Animal Physiology
- Enzyme Structure and Function
- Protein Degradation and Inhibitors
- Ion-surface interactions and analysis
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Treatment and Management
- Redox biology and oxidative stress
- Characterization and Applications of Magnetic Nanoparticles
- Peptidase Inhibition and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Force Microscopy Techniques and Applications
- Toxin Mechanisms and Immunotoxins
- Gold and Silver Nanoparticles Synthesis and Applications
- Nicotinic Acetylcholine Receptors Study
- Pancreatic function and diabetes
- Biochemical and Structural Characterization
- Protein Tyrosine Phosphatases
Novartis (Switzerland)
2024
Novartis Institutes for BioMedical Research
2024
Novartis (Germany)
2024
Max Planck Institute of Biochemistry
2013-2022
Max Planck Society
2013-2017
Significance Biological electron cryomicroscopy is limited by the radiation sensitivity of samples and consequent need to minimize exposure beam. This, in turn, results low-contrast images with a poor signal-to-noise ratio. The current practice improve phase contrast defocusing transfer functions necessitating image restoration provide interpretable data. Phase plates enable in-focus contrast, but existing ones, including thin film Zernike-type plate, suffer from severe limitations, such as...
With the advent of direct electron detectors, perspectives cryo-electron microscopy (cryo-EM) have changed in a profound way. These cameras are superior to previous detectors coping with intrinsically low contrast and beam-induced motion radiation-sensitive organic materials embedded amorphous ice, hence they enabled structure determination many macromolecular assemblies atomic or near-atomic resolution. Nevertheless, there still limitations one them is size target structure. Here, we report...
Targeted protein degradation (TPD) mediates level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only few have been utilized TPD. Interestingly, the workhorse ligase CRBN observed be downregulated settings resistance immunomodulatory inhibitory drugs (IMiDs). Here we show that essential receptor DCAF1 can harnessed utilizing selective,...
Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) receptors are critically important for metabolism, vascular tone, inflammatory response. AM also required normal lymphatic blood development angiogenesis. They play a pivotal role in embryo implantation fertility can provide protection against hypoxic oxidative stress. CGRP heterodimers of the receptor-like receptor (CLR) activity-modifying protein 1 (RAMP1) (CGRPR), as well RAMP2 or RAMP3 (AM
The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding how different peptides generate profound differences G protein-mediated signalling still lacking. Here we combine cryo-electron microscopy, molecular dynamics simulations, mutagenesis pharmacological assays, to interrogate the mechanism consequences binding four...
Abstract Cryo-EM of large, macromolecular assemblies has seen a significant increase in the numbers high-resolution structures since arrival direct electron detectors. However, sub-nanometre resolution cryo-EM are rare compared with crystal structure depositions, particularly for relatively small particles (<400 kDa). Here we demonstrate benefits Volta phase plates single-particle analysis by time-efficient determination 257 kDa human peroxiredoxin-3 dodecamers at 4.4 Å resolution. The...
Abstract The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding SecR binding activation is important its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, biochemical cross-linking to determine a 2.3 Å structure, interrogate bound the SecR:Gs complex. exhibited unique organization extracellular domain (ECD) relative 7-transmembrane (TM) core,...
Abstract The histone H3 variant CENP-A marks centromeres epigenetically and is essential for mitotic fidelity. Previous crystallographic studies of the nucleosome core particle (NCP) reconstituted with a human α-satellite DNA derivative revealed both ends to be highly flexible, feature important functions. However, recent cryo-EM NCP complexes comprising primarily Widom 601 reported well-ordered ends. Here, we report structure determined by Volta phase-plate imaging. data reveal that one...
ABSTRACT Our understanding of archaeal virus diversity and structure is just beginning to emerge. Here we describe a new virus, tentatively named Metallosphaera turreted icosahedral (MTIV), that was isolated from an acidic hot spring in Yellowstone National Park, USA. Two strains the were identified found replicate host species closely related yellowstonensis . Each strain encodes 9.8- 9.9-kb linear double-stranded DNA (dsDNA) genome with large inverted terminal repeats. 21 open reading...
With the advent of direct electron detectors, perspectives cryo-electron microscopy (cryo-EM) have changed in a profound way 1 . These cameras are superior to previous detectors coping with intrinsically low contrast radiation-sensitive organic materials embedded amorphous ice, and so they enabled structure determination several macromolecular assemblies atomic or near-atomic resolution. According one theoretical estimation, few thousand images should suffice for calculating proteins as...
Journal Article Combination of Different Techniques in Cryo-Electron Tomography with a Volta Phase Plate Get access Maryam Khoshouei, Khoshouei Department Molecular Structural Biology, Max-Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152, Martinsried, Germany Search other works by this author on: Oxford Academic Google Scholar Gunther Gerisch, Gerisch Cell Dynamics, Maria Ecke, Ecke Julio Ortiz, Ortiz Jiirgen M Plitzko, Plitzko Radostin Danev, Danev Wolfgang Baumeister...
ABSTRACT The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding how different peptides generate profound differences G protein-mediated signalling still lacking. Here we have combined cryo-electron microscopy, molecular dynamics simulations, mutagenesis pharmacological assays, to interrogate the mechanism consequences...
Journal Article Solution Conformations of Peroxiredoxins Visualised by Volta Phase Plates Get access Mazdak Radjainia, Radjainia Department Biochemistry and Molecular Biology, Monash University, Melbourne, Australia Search for other works this author on: Oxford Academic Google Scholar Maryam Khoshouei, Khoshouei Structural Max Planck Institute Biochemistry, Martinsried, Germany Matthew Belousoff, Belousoff Radostin Danev Microscopy Microanalysis, Volume 22, Issue S3, 1 July 2016, Pages...
Abstract Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. Numerous protein toxins have been identified that modulate Nav gating, structures of in complex with these helped elucidate the molecular mechanisms voltage-dependent channel gating. The deathstalker scorpion α-toxin LqhαIT exerts a strong action prolonging effect on channels. Biochemical studies show features functionally essential epitope at its C-terminus is not shared related...