A5085754881- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- Microbial Natural Products and Biosynthesis
- Trypanosoma species research and implications
- Biochemical and Molecular Research
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Advanced Electron Microscopy Techniques and Applications
- Plant biochemistry and biosynthesis
- Glycosylation and Glycoproteins Research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- Heat shock proteins research
- Integrated Circuits and Semiconductor Failure Analysis
- Galectins and Cancer Biology
- Calcium signaling and nucleotide metabolism
ETH Zurich
2014-2023
Institute of Molecular Biology and Biophysics
2015-2019
École Polytechnique Fédérale de Lausanne
2003-2013
Mammalian fatty acid synthase is a large multienzyme that catalyzes all steps of synthesis. We have determined its crystal structure at 3.2 angstrom resolution covering five catalytic domains, whereas the flexibly tethered terminal acyl carrier protein and thioesterase domains remain unresolved. The reveals complex architecture alternating linkers enzymatic domains. Substrate shuttling facilitated by flexible tethering domain limited contact between condensing modifying portions multienzyme,...
The structure provides insight into how protein synthesis is initiated and the evolution of eukaryotic ribosome.
Mammalian mitochondrial ribosomes (mitoribosomes) synthesize mitochondrially encoded membrane proteins that are critical for function. Here we present the complete atomic structure of porcine 55S mitoribosome at 3.8 angstrom resolution by cryo-electron microscopy and chemical cross-linking/mass spectrometry. The 28S subunit in complex was resolved 3.6 focused alignment, which allowed building a detailed including all its 15 mitoribosomal-specific proteins. reveals intersubunit contacts...
Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and subject more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation contains the nascent polypeptide exit tunnel. We present structure of 60S from Tetrahymena thermophila with initiation factor 6 (eIF6), cocrystallized antibiotic cycloheximide (a eukaryotic-specific inhibitor protein synthesis), at a...
Riboswitches are untranslated regions of messenger RNA, which adopt alternate structures depending on the binding specific metabolites. Such conformational switching regulates expression proteins involved in biosynthesis riboswitch substrates. Here, we present 2.9 angstrom–resolution crystal structure eukaryotic Arabidopsis thaliana thiamine pyrophosphate (TPP)–specific complex with its natural ligand. The specifically recognizes TPP via conserved residues located within two highly distorted...
Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis viral RNA-dependent polymerase and downstream proteins. Here, we present cryo-electron microscopy structure translating mammalian ribosome primed for on RNA. The adopts pseudoknot lodges at entry to messenger (mRNA) channel generate tension in mRNA promote frameshifting, whereas nascent polyprotein forms distinct...
We report crystal structures of the 2.6-megadalton alpha6beta6 heterododecameric fatty acid synthase from Thermomyces lanuginosus at 3.1 angstrom resolution. The alpha and beta polypeptide chains form six catalytic domains required for synthesis numerous expansion segments responsible extensive intersubunit connections. Detailed views all active sites provide insights into substrate specificities mechanisms reveal their unique characteristics, which are due to integration multienzyme. mode...
In the multifunctional fungal fatty acid synthase (FAS), acyl carrier protein (ACP) domain shuttles reaction intermediates covalently attached to its prosthetic phosphopantetheine group between different enzymatic centers of cycle. Here, we report structure Saccharomyces cerevisiae FAS determined at 3.1 angstrom resolution with ACP stalled active site ketoacyl synthase. The contacts base chamber through conserved, charge-complementary surfaces, which optimally position toward catalytic cleft...
Chloroplasts are cellular organelles of plants and algae that responsible for energy conversion carbon fixation by the photosynthetic reaction. As a consequence their endosymbiotic origin, they still contain own genome machinery protein biosynthesis. Here, we present atomic structure chloroplast 70S ribosome prepared from spinach leaves resolved cryo-EM at 3.4 Å resolution. The complete reveals features 4.5S rRNA, which probably evolved fragmentation 23S all five plastid-specific ribosomal...
Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found mitochondria Trypanosoma brucei, unicellular parasite that causes sleeping sickness humans. The trypanosomal mitoribosome features smallest rRNAs contains more proteins than all known shows how have taken over role scaffold from rRNA: They form an autonomous outer shell surrounds entire particle stabilizes positions...
Abstract Proteins that self-assemble into regular shell-like polyhedra are useful, both in nature and the laboratory, as molecular containers. Here we describe cryo-electron microscopy (EM) structures of two versatile encapsulation systems exploit engineered electrostatic interactions for cargo loading. We show increasing number negative charges on lumenal surface lumazine synthase, a protein naturally assembles ∼1-MDa dodecahedron composed 12 pentamers, induces stepwise expansion native...
Abstract Hepatitis C virus (HCV), a widespread human pathogen, is dependent on highly structured 5′-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation all proteins. The HCV IRES initiates by directly binding small ribosomal subunit (40S), circumventing need many eukaryotic initiation factors required mRNA scanning. Here we present cryo-EM structure 40S in complex with at 3.9 Å resolution, determined focused refinement an 80S ribosome–HCV...
Co-translational protein targeting to membranes is a universally conserved process. Central steps include cargo recognition by the signal particle and handover Sec translocon. Here we present snapshots of key co-translational-targeting complexes solved cryo-electron microscopy at near-atomic resolution, establishing molecular contacts between Escherichia coli translating ribosome, Our results reveal conformational changes that regulate latching sequence, release heterodimeric domains its...
Highlights•The high-resolution structure of the complete M. smegmatis 70S ribosome•Ribosomal proteins uncovered and located to antibiotic binding sites in ribosomal core•Unique surface features provide insight into polysomal translation Actinobacteria•The mycobacterial allows rational drug design for anti-tubercular therapySummaryThe ribosome carries out synthesis every living cell. It consequently represents a frontline target anti-microbial therapy. Tuberculosis ranks among leading causes...
Revolution in an RNA-packaging capsid Artificial nucleocapsid proteins, which could be analogous to those used by viruses package their genomes, are a promising way protect and deliver RNAs. Using escalating challenge nucleases, Tetter et al. evolved protein that forms multimeric, spherical cages into highly efficient selectively packages its own encoding RNA. Cryo–electron microscopy of the final design intermediates revealed stepwise expansion size, enabled destabilizing amino acid...
Abstract The translocon-associated protein (TRAP) complex resides in the endoplasmic reticulum (ER) membrane and interacts with Sec translocon ribosome to facilitate biogenesis of secretory proteins. TRAP plays a key role secretion many hormones, including insulin. Here we reveal molecular architecture mammalian how it engages translating associated Sec61 on ER membrane. is anchored via long tether its position further stabilized by finger-like loop. This positions cradle-like lumenal domain...