A5001260264- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Yersinia bacterium, plague, ectoparasites research
- Vibrio bacteria research studies
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- Bacillus and Francisella bacterial research
- Protein Structure and Dynamics
- Cancer-related Molecular Pathways
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Calcium Carbonate Crystallization and Inhibition
- Vector-borne infectious diseases
- Cancer Research and Treatments
- Clostridium difficile and Clostridium perfringens research
- Enzyme Structure and Function
- Plant nutrient uptake and metabolism
- Lysosomal Storage Disorders Research
- Advanced Electron Microscopy Techniques and Applications
- Plant-based Medicinal Research
- Metabolomics and Mass Spectrometry Studies
- Crystallization and Solubility Studies
- RNA modifications and cancer
- Force Microscopy Techniques and Applications
Max Planck Institute of Biochemistry
2019-2024
Center for Integrated Protein Science Munich
2017-2020
Technical University of Munich
2016-2020
Weizmann Institute of Science
2017-2018
Abstract The endoplasmic reticulum (ER) undergoes continuous remodelling via a selective autophagy pathway, known as ER-phagy 1 . receptors have central role in this process 2 , but the regulatory mechanism remains largely unknown. Here we report that ubiquitination of receptor FAM134B within its reticulon homology domain (RHD) promotes clustering and binding to lipidated LC3B, thereby stimulating ER-phagy. Molecular dynamics (MD) simulations showed how perturbs RHD structure model bilayers...
Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane (EMC), comprising eight conserved subunits, has emerged as a central player this process. Yet, we have limited understanding of how EMC enables insertion integrity diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast human cryo-EM structures reveal intricate assemblies human-specific features associated with pathologies. Structure-based functional...
Abstract Transmembrane E3 ligases play crucial roles in homeostasis. Much protein and organelle quality control, metabolic regulation, are determined by ER-resident MARCH6 ligases, including Doa10 yeast. Here, we present Doa10/MARCH6 structural analysis cryo-EM AlphaFold predictions, a structure-based mutagenesis campaign. The majority of adopts unique circular structure within the membrane. This channel is established lipid-binding scaffold, gated flexible helical bundle. ubiquitylation...
Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, unknown structures. was shown be cytotoxic likely involved pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures YaxA YaxB, together cryo-electron microscopy map complex. Our reveal pore...
Loss of function mutations in the PTEN-induced kinase 1 (PINK1) are causal for autosomal recessive Parkinson's disease (PD) whilst gain LRRK2 cause dominant PD. PINK1 indirectly regulates phosphorylation a subset Rab GTPases at conserved Serine111 (Ser111) residue within SF3 motif. Using genetic code expansion technologies, we have produced stoichiometric Ser111-phosphorylated Rab8A revealing impaired interactions with its cognate guanine nucleotide exchange factor and GTPase activating...
Salmonella infections require the delivery of bacterial effectors into host cell that alter regulation defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying Rab32 subfamily via cleaving regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization in complex with Rab32. Interestingly, solely processes inactive GDP-bound GTPase. crystal structure Rab32:GDP substrate...
Random microseed matrix screening (rMMS), in which seed crystals are added to random crystallization screens, is an important breakthrough soluble protein that increases the number of hits available for optimization. This greatly structures generated every year by typical structural biology laboratories. Inspired this success, rMMS has been adapted membrane proteins, making LCP stock scaling up conditions without changing physical and chemical parameters critical crystallization. Seed grown...
Abstract Loss of function mutations in the PINK1 kinase are causal for autosomal recessive Parkinson disease (PD) whilst gain LRRK2 cause dominant PD. indirectly regulates phosphorylation a subset Rab GTPases at conserved Serine111 (Ser111) residue within SF3 motif. Using genetic code expansion technologies we have produced stoichiometric Ser111-phosphorylated Rab8A revealing impaired interactions with its cognate guanine nucleotide exchange factor (GEF) and GTPase activating protein (GAP)....
Random Microseed Matrix-Screening (rMMS), where seed crystals are added automatically to random crystallization screens, is a significant recent breakthrough in protein [1].During the eight years since method was published, theoretical understanding of has increased [2 -4], and several important practical variations basic have emerged [5, 6].We will briefly describe some these variations, including cross-seeding, introduce novel making LCP stocks by scaling up conditions.We also generating...
Random Microseed Matrix-Screening (rMMS), where seed crystals are added automatically to random crystallization screens, is a significant recent breakthrough in protein [1].During the eight years since method was published, theoretical understanding of has increased [2], and several important practical variations basic have emerged [3].We will briefly describe some these variations, including cross-seeding, introduce novel making LCP stocks by scaling up conditions.[1]
Abstract Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane (EMC), comprising eight conserved subunits, has emerged as a central player this process. Yet, we have limited understanding of how EMC enables insertion integrity diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast human cryo-EM structures reveal intricate assemblies human-specific features associated with pathologies. Structure-based...