A5102851492- Nuclear Structure and Function
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- HIV Research and Treatment
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- Microbial Metabolic Engineering and Bioproduction
- Cytomegalovirus and herpesvirus research
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Biofuel production and bioconversion
- Metalloenzymes and iron-sulfur proteins
- Protein Structure and Dynamics
- Porphyrin Metabolism and Disorders
- Computational Drug Discovery Methods
- Lanthanide and Transition Metal Complexes
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Autophagy in Disease and Therapy
MRC Laboratory of Molecular Biology
2024
European Molecular Biology Laboratory
2019-2021
Max Planck Institute of Biophysics
2012-2021
Max Planck Society
2015
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...
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...
The introduction of direct electron detectors with higher detective quantum efficiency and fast read-out marks the beginning a new era in cryo-microscopy. Using FEI Falcon II detector video mode, we have reconstructed map at 3.36 Å resolution 1.2 MDa F420-reducing hydrogenase (Frh) from methanogenic archaea only 320,000 asymmetric units. Videos frames were aligned by combination image particle alignment procedures to overcome effects beam-induced motion. density shows all secondary structure...
The integrity of the nuclear membranes coupled to selective barrier pore complexes (NPCs) are essential for segregation nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation NPC assembly triggers an ESCRT-dependent surveillance system that seals pores: how these pores sensed sealed is ill defined. Using a budding yeast model, we show ESCRT Chm7 integral inner (INM) protein Heh1 spatially segregated by transport, with being actively exported Xpo1/Crm1. Thus, exposure INM...
Paclitaxel is a microtubule stabilising drug used to treat breast, ovarian, and lung cancers. Its anticancer mechanism thought rely on mitotic arrest of fast-dividing cells subsequent apoptosis following spindle disruption. However, paclitaxel reduces tumour size even in slow-dividing tumours, indicating an alternative, poorly characterised interphase. Understanding the less effects important for more effective cancer treatments, reducing resistance toxicity healthy cells. Here, we found...
Abstract Nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins that form an intricate cylindrical architecture around aqueous central channel. This is highly dynamic in space time. Variations NPC diameter were reported, but physiological circumstances molecular details remain unknown. Here we combined cryo-electron tomography subtomogram averaging with integrative structural modeling to capture...
Abstract 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 demonstrate NPC cellulo...
The 'Bayesian inference of electron microscopy' (BioEM) framework makes it possible to determine the stoichiometry protein complexes using 3D coarse-grained models and a relatively small number cryo-electron microscopy images as input. We applied method most probable rotor ring archaeal Na+ ATP synthase from Pyrococcus furiosus, multisubunit complex able produce under extreme conditions. Archaeal synthases consist catalytic A1 part membrane-embedded AO portion. portion is composed a-subunit....
Summary Nuclear pore complexes (NPCs) mediate exchange across the nuclear envelope. They consist of hundreds proteins called nucleoporins (Nups) that assemble in multiple copies to fuse inner and outer membranes. Elucidating molecular function architecture NPCs imposes a formidable challenge requires convergence vitro situ approaches. How exactly NPC accommodates processes such as mRNA export or assembly turnover inside cells remains poorly understood. Here we combine integrated structural...
Abstract Nuclear pore complexes (NPCs) are nuclear gateways which regulate the transit of molecules larger than 40kDa through a Ran-dependent transport 1 . The somatic human NPC scaffold consists three stacked rings: cytoplasmic (CR), nucleoplasmic (NR), and inner ring (IR), define central channel approximately 55nm wide 2 Although many studies have investigated architecture 3 , it remains largely unknown how accommodates different functions non-somatic cells. Here, we reveal in-cell sperm...
Abstract The integrity of the nuclear envelope membranes coupled to diffusion barrier and selective transport properties pore complexes (NPCs) are a prerequisite for robust segregation nucleoplasm cytoplasm. Recent work supports that mechanical membrane disruption or perturbation NPC assembly can trigger an ESCRT-dependent surveillance system seals pores: how these pores sensed sealed remains be fully defined. Here, we show principal components in yeast, which includes ESCRT Chm7 integral...