A5068682504- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Complement system in diseases
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Nuclear Structure and Function
- Advanced Electron Microscopy Techniques and Applications
- Cellular transport and secretion
- Mosquito-borne diseases and control
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Vibrio bacteria research studies
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- ATP Synthase and ATPases Research
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Digestive system and related health
Spanish National Cancer Research Centre
2018-2024
Institut Curie
2023-2024
University of Exeter
2023-2024
Centro de Investigación del Cáncer
2021-2024
Cancer Research Center
2023-2024
Institut de Biologie Intégrative de la Cellule
2023-2024
University of Antwerp
2023-2024
Living Systems (United States)
2023-2024
Cornell University
2023-2024
Weill Cornell Medicine
2023-2024
Abstract In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic on host cells activate signalling pathways. Previous studies have described structures of individual components and subcomplexes; molecular details its assembly mechanism action remain unresolved. Here we report electron cryo-microscopy structure human at subnanometre...
Microtubules are essential for intracellular organization and chromosome segregation. They nucleated by the γ-tubulin ring complex (γTuRC). However, isolated vertebrate γTuRC adopts an open conformation that deviates from microtubule structure, raising question of nucleation mechanism. In this study, we determined cryo-electron microscopy structures human bound to a nascent microtubule. Structural changes into closed ensure templates 13-protofilament microtubules exist in cells. Closure is...
Abstract The membrane attack complex (MAC) is one of the immune system’s first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis self-cells. How MAC disrupts barrier remains unclear. Here we use electron cryo-microscopy flicker spectroscopy show interacts with lipid bilayers in two distinct ways. Whereas C6 C7 associate outer leaflet reduce energy for bending, C8 C9 traverse bilayer increasing rigidity. CryoEM...
RUVBL1-RUVBL2 regulates assembly of microtubule nucleator γ-tubulin ring complex and allows its recombinant production.
The structure of the unique bacterial tubulin BtubA/B from Prosthecobacter is very similar to eukaryotic αβ-tubulin but, strikingly, fold without chaperones. Our sequence comparisons indicate that BtubA and BtubB do not really correspond either α- or β-tubulin but have mosaic sequences with intertwining features both. Their nucleotide-binding loops are more conserved, their divergent discrete surface zones involved in microtubule assembly binding cytosolic chaperonin, which absent dejongeii...
Tubulin proteostasis is regulated by a group of molecular chaperones termed tubulin cofactors (TBC). Whereas heterodimer formation well-characterized biochemically, its dissociation pathway not clearly understood. We carried out biochemical assays to dissect the role human TBCE and TBCB in αβ-tubulin dissociation. used electron microscopy image processing determine three-dimensional structure TBCE, α-tubulin (αEB) complex, which formed via two chaperones. Docking atomic structures domains...
MicrosymposiaC25 MS density map using the MDFF method (Molecular Dynamics Flexible Fitting).The structure allowed for identification of ribosomelipid interactions.The rRNA helix 59 (H59) directly contacts lipid surface and appears to modulate membrane in immediate vicinity proposed lateral gate PCC.Based on our molecular dynamics simulations we present a model signal anchor-gated PCC membrane.
Colchicine has been used to treat gout and, more recently, effectively prevent autoinflammatory diseases and both primary recurrent episodes of pericarditis. The anti-inflammatory action colchicine seems result from irreversible inhibition tubulin polymerization microtubule (MT) assembly by binding the heterodimer, avoiding signal transduction required activation entire NLRP3 inflammasome. Emerging results show that MT network is a potential regulator cardiac mechanics. Here, we investigated...
Abstract The membrane attack complex (MAC) is one of the immune system’s first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis self-cells. How MAC disrupts barrier remains unclear. Here we use electron cryo-microscopy flicker spectroscopy show interacts with lipid bilayers in two distinct ways. Whereas C6 C7 associate outer leaflet reduce energy for bending, C8 C9 traverse bilayer increasing rigidity. CryoEM...
Abstract The activity of dynein is regulated by a number adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. regulation consequently central physiology but remains largely unexplored. We now describe one best-known adaptors, BICD2, activated through phosphorylation. In G2, phosphorylation BICD2 CDK1 promotes PLK1. turn, PLK1 single residue in N-terminus results structural change facilitates and allowing...
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of wide range physiological transcripts. RUVBL1 RUVBL2 AAA-ATPases form an hetero-hexameric ring part several macromolecular complexes such as INO80, SWR1, R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity required for NMD activation by unknown mechanism. Here, we show DHX34, RNA helicase regulating initiation, directly interacts with in vitro cells. Cryo-EM reveals...
Abstract Biogenesis of the U5 small nuclear ribonucleoprotein (snRNP) is an essential and highly regulated process. In particular, PRPF8, one snRNP main components, requires HSP90 working in concert with R2TP, a cochaperone complex containing RUVBL1 RUVBL2 AAA-ATPases, additional factors that are still poorly characterized. Here, we use biochemistry, interaction mapping, mass spectrometry cryoEM to study role ZNHIT2 regulation R2TP chaperone during biogenesis PRPF8. forms which depends...
Eukaryotic ectotherms of the Southern Ocean face energetic challenges to protein folding assisted by cytosolic chaperonin CCT. We hypothesize that CCT and its client proteins (CPs) have co-evolved molecular adaptations facilitate CCT-CP interaction ATP-driven cycle at low temperature. To test this hypothesis, we compared functional structural properties systems from testis tissues an Antarctic fish, Gobionotothen gibberifrons (Lönnberg) (habitat/body T = -1.9 +2°C), cow (body 37°C). examined...
Abstract Some long noncoding (lnc)RNAs harbor the potential to produce functional micropeptides. Despite increasing recognition of their significance, regulatory dynamics cytoplasmic lncRNA expression, decay, and translation remain poorly understood. Here, we investigate role ribonucleases in controlling levels lncRNAs. By transcriptomic analysis identified DIS3 but not XRN1 as a major enzyme preventing accumulation lncRNAs cytoplasm. Single-molecule experiments illustrate an example...
SUMMARY SETD8 is a methyltransferase that overexpressed in several cancers, which monomethylates H4K20 as well other non-histone targets such PCNA or p53. We here report novel inhibitors, were discovered while trying to identify chemicals prevent 53BP1 foci formation, an event mediated by methylation. Consistent with previous reports, inhibitors induce p53 expression, although they are equally toxic for p53-deficient cells. Thermal stability proteomics revealed the compounds had particular...
Abstract Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of wide range physiological transcripts. RUVBL1 RUVBL2 AAA-ATPases form an hetero-hexameric ring part several macromolecular complexes such as INO80, SWR1 R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity required for NMD activation by unknown mechanism. Here, we show DHX34, RNA helicase regulating initiation, directly interacts with in vitro cells. Cryo-EM...
Summary The activity of dynein is regulated by a number adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. regulation consequently central physiology, but remains largely unexplored. We now describe one best-known adaptors, BICD2, activated through phosphorylation. In G2 phosphorylation BICD2 CDK1 promotes PLK1. turn, PLK1 single residue in N-terminus results conformational change facilitates and...