- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Methane Hydrates and Related Phenomena
- Seismic Waves and Analysis
- Seismology and Earthquake Studies
- Bacteriophages and microbial interactions
- Genomics and Chromatin Dynamics
- Bacterial Genetics and Biotechnology
- Advanced Electron Microscopy Techniques and Applications
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Electron and X-Ray Spectroscopy Techniques
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Advanced biosensing and bioanalysis techniques
- Earthquake Detection and Analysis
- RNA Interference and Gene Delivery
- Photoreceptor and optogenetics research
- Ion Channels and Receptors
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Viral gastroenteritis research and epidemiology
- Hemoglobin structure and function
Pennsylvania State University
2019-2024
Universidad del Noreste
2024
University of California, San Francisco
2014-2019
Howard Hughes Medical Institute
2018
Center for Integrated Protein Science Munich
2009-2014
Ludwig-Maximilians-Universität München
2009-2013
The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that single copy may serve as an active PCC. We determined subnanometer-resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, we found in both idle states, the not oligomeric interacts mainly via two cytoplasmic loops universal ribosomal adaptor site....
Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation upstream TnaC leader peptide, a process for which interactions between nascent chain and ribosomal exit tunnel are critical. We determined 5.8 angstrom-resolution cryo-electron microscopy single-particle reconstruction stalled tnaC gene. The was extended within tunnel, making contacts with components at distinct sites. Upon stalling, two conserved residues peptidyltransferase center...
Protein biosynthesis, the translation of genetic code into polypeptides, occurs on ribonucleoprotein particles called ribosomes. Although X-ray structures bacterial ribosomes are available, high-resolution eukaryotic 80S lacking. Using cryoelectron microscopy and single-particle reconstruction, we have determined structure a translating plant ( Triticum aestivum ) ribosome at 5.5-Å resolution. This map, together with 6.1-Å map Saccharomyces cerevisiae ribosome, has enabled us to model ∼98%...
Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger size than their bacterial counterparts due part to presence 80 r proteins rather 54 bacteria. Using cryoelectron microscopy reconstructions a translating plant ( Triticum aestivum ) 80S ribosome at 5.5-Å resolution, together with 6.1-Å map Saccharomyces cerevisiae ribosome, we have localized and modeled...
Cross-talk between histone modifications Histone play pivotal roles within the intricate protein networks that underlie transcription and gene silencing in eukaryotic genomes. The enzymes deposit them undergo spatiotemporal fine-tuning of their catalytic activity; one example is trans-histone cross-talk, which modification activates an enzyme responsible for another modification. Valencia-Sánchez et al. show H4 lysine 16 acetylation (H4K16ac), a hallmark decondensed, transcriptionally...
The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid tug-of-war is unclear. Furthermore, couples histone octamer deformation to nucleosome sliding, but underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture potential reaction intermediates. In one structure, residues near dyad and in H2A-H2B acidic patch, distal active protomer, appear disordered. disordered patch...
Abstract Correction of electron beam-induced sample motion is one the major factors contributing to recent resolution breakthroughs in cryo-electron microscopy. Improving accuracy and efficiency correction can lead further improvement. Based on observations that beam induces doming thin vitreous ice layer, we developed an algorithm correct anisotropic image at single pixel level across whole frame, suitable for both particle tomographic images. Iterative, patch-based detection combined with...
In all living cells, protein synthesis occurs on ribonucleoprotein particles called ribosomes. Molecular models have been reported for complete bacterial 70S and eukaryotic 80S ribosomes; however, only molecular of large 50S subunits archaea. Here, we present a model the Pyrococcus furiosus ribosome based 6.6 Å cryo-electron microscopy map. Moreover, determined reconstructions Euryarchaeota Methanococcus igneus Thermococcus kodakaraensis ribosomes Crenarchaeota Staphylothermus marinus...
Sirtuin 6 (SIRT6) is a multifaceted protein deacetylase/deacylase and major target for small-molecule modulators of longevity cancer. In the context chromatin, SIRT6 removes acetyl groups from histone H3 in nucleosomes, but molecular basis its nucleosomal substrate preference unknown. Our cryo–electron microscopy structure human complex with nucleosome shows that catalytic domain pries DNA entry-exit site exposes N-terminal helix, while zinc-binding binds to acidic patch using an arginine...