A5028999855- RNA Research and Splicing
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Advanced Proteomics Techniques and Applications
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Electron and X-Ray Spectroscopy Techniques
- RNA regulation and disease
- Molecular Biology Techniques and Applications
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- HIV Research and Treatment
- Renal and related cancers
- Microbial Metabolic Engineering and Bioproduction
- Reproductive Biology and Fertility
- Advanced Fluorescence Microscopy Techniques
Max Planck Institute of Biophysics
2019-2025
Goethe University Frankfurt
2023-2025
Norwegian University of Science and Technology
2024
European Molecular Biology Laboratory
2014-2023
European Molecular Biology Laboratory
2011-2023
University of Stuttgart
1992-2020
Norsk Hydro (Germany)
2020
European Molecular Biology Organization
2014-2016
European Bioinformatics Institute
2012-2013
GATC Biotech (Germany)
2012
The generation of mathematical models biological processes, the simulation these processes under different conditions, and comparison integration multiple data sets are explicit goals systems biology that require knowledge absolute quantity system's components. To date, systematic estimates cellular protein concentrations have been exceptionally scarce. Here, we provide a quantitative description proteome commonly used human cell line in two functional states, interphase mitosis. We show...
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and the primary focus vaccine development. In this study, we combined cryo-electron tomography, subtomogram averaging, molecular dynamics simulations to structurally analyze S in situ. Compared with recombinant S, viral was more heavily glycosylated occurred mostly closed prefusion conformation. We show that stalk domain contains three hinges, giving head unexpected orientational...
Nuclear pore complexes (NPCs) are gateways for nucleocytoplasmic exchange. To analyze their structure in a close-to-life state, we studied transport-active, intact nuclei from Dictyostelium discoideum by means of cryoelectron tomography. Subvolumes the tomograms containing individual NPCs were extracted silico and subjected to three-dimensional classification averaging, whereby distinct structural states observed. The central plug/transporter (CP/T) was variable volume could occupy different...
The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis homogeneous protein complexes. We gained distance restraints on a modular interaction network complexes affinity-purified from human cells applying an adapted XL-MS protocol. Systematic phosphatase 2A (PP2A) identified 176 interprotein 570 intraprotein cross-links that link specific trimeric PP2A to multitude adaptor proteins control their cellular...
Highlights•The human NPC is resolved up to 3.2 nm•32 copies of the hNup107 subcomplex form two reticulated rings•Mitotic phosphorylation sites cluster into intersubcomplex contacts•The hNup214 forms a protrusion at cytoplasmic ringSummaryThe nuclear pore complex (NPC) fundamental component all eukaryotic cells that facilitates nucleocytoplasmic exchange macromolecules. It assembled from multiple about 30 nucleoporins. Due its size and composition, determining structure an enormous challenge,...
Abstract A better understanding of proteostasis in health and disease requires robust methods to determine protein half-lives. Here we improve the precision accuracy peptide ion intensity-based quantification, enabling more accurate turnover determination non-dividing cells by dynamic SILAC-based proteomics. This approach allows exact half-lives ranging from 10 >1000 h. We identified 4000–6000 proteins several cell types, corresponding 9699 unique identifications over entire data set....
To understand the structure and function of large molecular machines, accurate knowledge their stoichiometry is essential. In this study, we developed an integrated targeted proteomics super‐resolution microscopy approach to determine absolute human nuclear pore complex (NPC), possibly largest eukaryotic protein complex. We show that NPC has a previously unanticipated varies across cancer cell types, tissues in disease. Using large‐scale proteomics, provide evidence more than one third...
Blueprint for a macromolecular machine Nuclear pore complexes (NPCs) consist of around 1000 protein subunits, are embedded in the membrane that surrounds nucleus, and regulate transport between nucleus cytoplasm. Although overall shape NPCs is known, details this complex have been obscure. Now, Lin et al. reconstituted components, determined interactions them, fitted them into tomographic reconstruction. Kosinski provided an architectural map inner ring pore. Science , issue pp....
Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size HIV-1 is generally believed to exceed diameter pore complex (NPC), indicating that has occur prior import. Here, we combined correlative light electron microscopy with subtomogram averaging capture structural status reverse transcription-competent complexes in infected T cells. We demonstrated NPC cellulo sufficient...
Abstract Exosomes are small secreted vesicles that can transfer their content to recipient cells. In cancer, exosome secretion has been implicated in tumor growth and metastatic spread. this study, we explored the possibility exosomal pathways might discard tumor-suppressor miRNA restricts progression. Secreted characterized from isogenic bladder carcinoma cell lines with differing potential were uncoupled binding target transcripts or AGO2–miRISC complex. cells, observed a relative increase...
In eukaryotic cells, nuclear pore complexes (NPCs) fuse the inner and outer membranes mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins form a cylindrical architecture around an aqueous central channel. This is highly dynamic in space time. Variations NPC diameter have been reported, but physiological circumstances molecular details remain unknown. Here, we combined cryo–electron tomography with integrative structural modeling to capture movie respective...
INTRODUCTION The eukaryotic nucleus pro-tects the genome and is enclosed by two membranes of nuclear envelope. Nuclear pore complexes (NPCs) perforate envelope to facilitate nucleocytoplasmic transport. With a molecular weight ∼120 MDa, human NPC one larg-est protein complexes. Its ~1000 proteins are taken in multiple copies from set about 30 distinct nucleoporins (NUPs). They can be roughly categorized into classes. Scaf-fold NUPs contain folded domains form cylindrical scaffold...