A5001113054- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Biochemical Acid Research Studies
- Photosynthetic Processes and Mechanisms
- Genetic Neurodegenerative Diseases
- Microtubule and mitosis dynamics
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Sperm and Testicular Function
- Advanced Proteomics Techniques and Applications
- Adipose Tissue and Metabolism
- Protist diversity and phylogeny
- Complement system in diseases
- Protein Structure and Dynamics
- ATP Synthase and ATPases Research
- Cell death mechanisms and regulation
- Reproductive Biology and Fertility
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
Utrecht University
2020-2024
Agency for Science, Technology and Research
2022
Netherlands Metabolomics Centre
2021-2022
National University of Singapore
2022
Singapore Immunology Network
2022
European Molecular Biology Laboratory
2018-2021
Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which increasing globally. are powered by a microtubule-based molecular machine—the axoneme—but it unclear how axonemal microtubules ornamented support diverse fertilization environments. Here, we present high-resolution structures of native doublet (DMTs) from sea urchin and bovine sperm, representing external internal fertilizers. We identify >60 proteins...
Article24 July 2018Open Access Transparent process Thermal proteome profiling in bacteria: probing protein state vivo André Mateus orcid.org/0000-0001-6870-0677 Genome Biology Unit, European Molecular Laboratory, Heidelberg, Germany Search for more papers by this author Jacob Bobonis Faculty of Biosciences, Heidelberg University, Nils Kurzawa orcid.org/0000-0002-7846-2817 Frank Stein Proteomics Core Facility, Dominic Helm Johannes Hevler Athanasios Typas Corresponding Author [email...
The mammalian respiratory chain complexes I, III
Significance Spatial organization of mitochondria is vital for cellular function. In many specialized cell types, are immobilized at specific subcellular loci through interactions with the cytoskeleton. One most striking mitochondrial configurations occurs in mammalian sperm, where wrap around flagellum. Malformation sheath causes infertility, but molecular structures underlying this intricate arrangement unknown. Here, we analyzed sperm from three species. We find that although dimensions...
Abstract Huntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form HTT. Both wildtype and disease-state HTT hetero-dimer with HAP40 unknown functional relevance. We demonstrate vivo cell models that cellular abundance are coupled. Integrating data 2.6 Å cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, modeling, we provide near-atomic-level view HTT, its...
Abstract Cross‐linking mass spectrometry has developed into an important method to study protein structures and interactions. The in‐solution cross‐linking workflows involve time sample consuming steps do not provide sensible solutions for differentiating cross‐links obtained from co‐occurring oligomers, complexes, or conformers. Here we a workflow combining blue native PAGE with in‐gel (IGX‐MS). This circumvents steps, such as buffer exchange cross‐linker concentration optimization....
Abstract In response to improper kinetochore-microtubule attachments in mitosis, the spindle assembly checkpoint (SAC) assembles mitotic complex (MCC) inhibit anaphase-promoting complex/cyclosome, thereby delaying entry into anaphase. The MCC comprises Mad2:Cdc20:BubR1:Bub3. Its is catalysed by unattached kinetochores on a Mad1:Mad2 platform. Mad1-bound closed-Mad2 (C-Mad2) recruits open-Mad2 (O-Mad2) through self-dimerization. This interaction, combined with Mps1 kinase-mediated...
The tricarboxylic acid cycle is the central pathway of energy production in eukaryotic cells and plays a key part aerobic respiration throughout all kingdoms life. One pivotal enzymes this 2-oxoglutarate dehydrogenase complex (OGDHC), which generates NADH by oxidative decarboxylation to succinyl-CoA. OGDHC megadalton protein originally thought be assembled from three catalytically active subunits (E1o, E2o, E3). In fungi animals, however, MRPS36 has more recently been proposed as putative...
Combining mass spectrometry-based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes oxidative phosphorylation found that dimeric apoptosis-inducing factor 1 (AIFM1) forms a defined complex with ∼10% monomeric cytochrome
Single-gene deletions can affect the expression levels of other genes in same operon bacterial genomes. Here, we used proteomics for 133 Escherichia coli gene deletion mutants and transcriptome sequencing (RNA-seq) data from 71 to probe extent transcriptional post-transcriptional effects operons. Transcriptional were common on located downstream consistent across all members, with nearly 40% operons showing greater than 2-fold up- or downregulation. Surprisingly, observed an additional...
Abstract To find and fuse with the egg, mammalian sperm must complete an arduous voyage through female reproductive tract. The cell’s remarkable odyssey is powered by its flagellum, a microtubule-based molecular machine ornamented accessory structures that stabilize tail in viscous media. Recently, cryo-electron tomography (cryo-ET) revealed flagella are further reinforced at scale sperm-specific microtubule inner proteins (sperm-MIPs), but identities of these sperm-MIPs unknown. Here, we...
Mitochondria are densely packed with proteins, of which most involved physically or more transiently in protein-protein interactions (PPIs). host among others all enzymes the Krebs cycle and oxidative phosphorylation pathway foremost associated cellular bioenergetics. However, mitochondria also important contributors to apoptotic cell death contain their own genome indicating that they play additionally an eminent role processes beyond Despite intense efforts identifying characterizing...
Abstract The human complement system provides a first line of defence against pathogens. It requires well‐orchestrated sequential assembly an array terminal components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC). Although much information about MAC is available, structure soluble C7 has remained elusive. proteins C6 share very high sequence homology exhibit several conserved domains, disulphide bridges, C‐mannosylation sites. Here, we used integrative...
Abstract In response to improper kinetochore-microtubule attachments in mitosis, the spindle assembly checkpoint (SAC) assembles mitotic complex (MCC) inhibit anaphase- promoting complex/cyclosome, thereby delaying entry into anaphase. The MCC is a of Mad2, Cdc20 and BubR1:Bub3. Its catalysed by unattached kinetochores on catalytic Mad1:Mad2 platform. Mad1-bound closed-Mad2 (C-Mad2) recruits open-Mad2 (O- Mad2) through self-dimerization. This interaction, combined with Mps1 kinase-mediated...
Summary Mitochondria-cytoskeleton interactions modulate cellular physiology by regulating mitochondrial transport, positioning, and immobilization. However, there is very little structural information defining mitochondria-cytoskeleton interfaces in any cell type. Here, we use cryo-focused ion beam milling-enabled cryo-electron tomography to image mammalian sperm, where mitochondria wrap around the ciliary cytoskeleton. We find that are tethered their neighbors through inter-mitochondrial...
SUMMARY The mammalian respiratory chain complexes I, III 2 and IV (CI, CIII CIV) are critical for cellular bioenergetics form a stable assembly, the respirasome (CI- -CIV), that is biochemically structurally well documented. role of in regulation metabolism subject to intense debate difficult study because individual coexist together with high levels respirasomes. To critically investigate vivo respirasome, we generated homozygous knock-in mice have normal but profoundly decreased...
Abstract Huntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form HTT. Both wildtype and disease-state HTT hetero-dimer with HAP40 unknown functional relevance. We demonstrate vivo that cellular abundance are coupled. Integrating data 2.6 Å cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, modeling, we provide near-atomic-level view HTT, its molecular...