A5039505777- Lipid Membrane Structure and Behavior
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Sphingolipid Metabolism and Signaling
- Fungal and yeast genetics research
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Endoplasmic Reticulum Stress and Disease
- Trypanosoma species research and implications
- Mosquito-borne diseases and control
- Toxoplasma gondii Research Studies
- Muscle Physiology and Disorders
- Click Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Eicosanoids and Hypertension Pharmacology
- Chemical Synthesis and Analysis
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
École Polytechnique Fédérale de Lausanne
2019-2024
European Molecular Biology Laboratory
2017-2023
European Molecular Biology Laboratory
2020-2023
European Molecular Biology Laboratory
2022
University of Geneva
2013-2015
NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry
2013
Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which involved sphingolipid biosynthesis, are associated with intellectual disability, but pathogenic mechanism remains obscure. Here, we characterize 31 individuals de novo missense variants CERT1. Several fall into a previously uncharacterized dimeric helical domain that enables...
Dynamic amphiphiles are with dynamic covalent bridges between their hydrophilic heads and hydrophobic tails. Their usefulness to activate ion transporters, for odorant release, differential sensing of odorants perfumes, has been demonstrated recently. Here, we report that the same "fragrant" ideal screen new siRNA transfection agents. The advantages this approach include rapid access fairly large libraries complex structures, possible transformation en route assist uptake minimize toxicity....
STARD4 regulates cholesterol homeostasis by transferring between the plasma membrane and endoplasmic reticulum. The structure features a helix-grip fold surrounding large hydrophobic cavity holding sterol. Its access is controlled gate formed Ω1 Ω4 loops C-terminal α-helix. Little known about mechanisms which binds to membranes extracts/releases cholesterol. All available structures of are without bound sterol display same closed conformation gate. transfer activity mouse enhanced in...
The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias have a dramatically signaling network, despite similar kinase activity. To provide molecular rationale for these observations, we study Dbl-homology (DH) Pleckstrin-homology (PH) domains p210, which constitute only structural differences to p190. Here report high-resolution structures DH PH characterize conformations DH-PH unit in solution. Our functional analyses show no evidence that...
Article13 September 2021Open Access Source DataTransparent process GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis Prathyush Pothukuchi orcid.org/0000-0002-6242-2319 Institute Biochemistry and Cell Biology, National Research Council Italy, Rome, Italy Search for more papers by this author Ilenia Agliarulo These authors contributed equally work Marinella Pirozzi Riccardo Rizzo Domenico Russo Gabriele Turacchio Julian Nüchel...
Huntington disease is a neurodegenerative characterised by polymorphic tract of polyglutamine repeats in exon 1 the huntingtin protein, which thought to be responsible for protein aggregation and neuronal death. The preceded 17-residue sequence that intrinsically disordered. This region subject phosphorylation, acetylation other post-translational modifications vivo, modulate its secondary structure, subcellular localisation. We used Molecular Dynamics simulations with novel...
MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes eukaryotes. Despite this ubiquity, they remain poorly characterised at structural functional level compared to other common repeats. In terms, are often assumed be lipid-binding modules that mediate membrane targeting. We addressed putative activity by focusing on protein composed solely of repeats— Trypanosoma brucei MORN1. Surprisingly, no evidence for...
Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators actomyosin contractility in cells. The DMPK MRCK1 is required for activation myosin, leading to development cortical tension, apical constriction, and early gastrulation. Here, we present structure, conformation, membrane-binding properties Caenorhabditis elegans MRCK1. forms a homodimer with N-terminal domains, parallel coiled coil 55 nm, C-terminal tripartite module C1, pleckstrin homology (PH),...
Abstract Lipid Transfer Proteins (LTPs) are key players in cellular homeostasis and regulation, as they coordinate the exchange of lipids between different organelles. Despite their importance, our mechanistic understanding how LTPs function at molecular level is still its infancy, mostly due to large number existing low degree conservation sequence structural level. In this work, we use simulations characterize dynamical aspects a representative dataset Transport Domains (LTDs) 12 that...
Lipid transfer proteins (LTPs) are key players in cellular homeostasis and regulation, as they coordinate the exchange of lipids between different organelles. Despite their importance, our mechanistic understanding how LTPs function at molecular level is still its infancy, mostly due to large number existing low degree conservation sequence structural level. In this work, we use simulations characterize a representative dataset lipid transport domains (LTDs) 12 that belong 8 distinct...
Huntington's disease is a neurodegenerative disorder caused by an expanded polyglutamine stretch near the N-terminus of huntingtin (HTT) protein, rendering protein more prone to aggregate. The first 17 residues in HTT (Nt17) interact with lipid membranes and harbor multiple post-translational modifications (PTMs) that can modulate conformation aggregation. In this study, we used combination biophysical studies molecular simulations investigate effect PTMs on helicity Nt17 presence various...
Lipid transfer proteins (LTPs) maintain the specialised lipid compositions of biological membranes, and many are associated with disease. In eukaryotes, they support organellar functions by transporting lipids between compartmentalised metabolic pathways. However, for majority hundreds human LTPs, cargoes remain unknown. We combined biochemical, lipidomic computational methods to characterize LTP-lipid complexes assembled in cellulo an vitro biochemical assay. identified bound about half...
ABSTRACT MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes eukaryotes. Despite this ubiquity, they remain poorly characterised at structural functional level compared to other common repeats. In terms, are often assumed be lipid-binding modules that mediate membrane targeting. We addressed putative activity by focusing on protein composed solely of repeats – Trypanosoma brucei MORN1. Surprisingly, no evidence...
Abstract Glycans are important regulators of cell and organismal physiology. This requires that the glycan biosynthesis be controlled to achieve specific cellular profiles. assembled in Golgi apparatus on secretory cargoes traverse it. The mechanisms by which ensures cell- cargo-specific glycosylation remain obscure. We investigated how regulates studying glycosphingolipids, glycosylated lipids with critical roles signalling differentiation. identified matrix protein GRASP55 as a controller...
Abstract STARD4 regulates cholesterol homeostasis by transferring between plasma membrane and endoplasmic reticulum. The structure features a helix-grip fold surrounding large hydrophobic cavity holding the sterol. Its access is controlled gate formed two flexible loops - Ω1 Ω4- C-terminal α-helix. Besides this, little known about mechanisms which binds to membranes extract/releases cholesterol. All available structures of are without bound sterol display same closed conformation gate....
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine stretch near the N-terminus of huntingtin (HTT) protein, rendering protein more prone to aggregate. The first 17 residues in HTT (Nt17) interact with lipid membranes and harbor multiple posttranslational modifications (PTMs) that can modulate conformation aggregation. In this study, we used combination biophysical studies molecular simulations investigate impact PTMs on helicity Nt17...
Summary Remodeling of the cytoskeleton underlies myriad processes essential for life. Protein kinases DMPK family are critical regulators actomyosin contractility in cells. In nematode worm, Caenorhabditis elegans , MRCK1 is required activation myosin, leading to development cortical tension, apical constriction and early gastrulation. Here, we present structure, conformation, membrane-binding properties C. MRCK1. forms an obligate homodimer with N-terminal kinase domains, a parallel...
SummaryRemodeling of the cytoskeleton underlies myriad processes essential for life. Protein kinases DMPK family are critical regulators actomyosin contractility in cells. In nematode worm, Caenorhabditis elegans, MRCK1 is required activation myosin, leading to development cortical tension, apical constriction and early gastrulation. Here, we present structure, conformation, membrane-binding properties C. elegans MRCK1. forms an obligate homodimer with N-terminal kinase domains, a parallel...