A5066717627- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Microtubule and mitosis dynamics
- Parasitic Infections and Diagnostics
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Protist diversity and phylogeny
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Methane Hydrates and Related Phenomena
- Insect symbiosis and bacterial influences
- Metabolism and Genetic Disorders
- Advanced Fluorescence Microscopy Techniques
- Tuberculosis Research and Epidemiology
- Plant Virus Research Studies
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Genetics, Aging, and Longevity in Model Organisms
New York University
2017-2025
Johns Hopkins University
2024-2025
University School
2020-2024
Office of Science
2024
Palo Alto Institute
2023
Stanford University
2023
New York Proton Center
2023
Indiana University School of Medicine
2022-2023
NYU Langone Health
2023
University of California, San Francisco
2008-2017
Influenza virus presents an important and persistent threat to public health worldwide, current vaccines provide immunity viral isolates similar the vaccine strain. High-affinity antibodies against a conserved epitope could diverse influenza subtypes protection future pandemic viruses. Cocrystal structures were determined at 2.2 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with major surface antigen (hemagglutinin, HA) from viruses responsible 1918...
Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification V(H)1-69 antibodies that broadly neutralize almost all A group 1 viruses constituted a breakthrough in the field. Here, we report isolation and characterization human monoclonal antibody CR8020 with broad neutralizing activity most 2 viruses, including H3N2 H7N7, which cause severe infection. crystal structure Fab 1968 pandemic H3 hemagglutinin (HA) reveals highly conserved...
How dynein makes the right moves The molecular motor cytoplasmic a wide range of different intracellular cargoes. Dynein's activity in vivo requires another protein, dynactin, but exactly why that should be has been very unclear. Although vitro experiments have provided some evidence dynactin increases dynein's processivity, resulting motility never come close to matching cargo-transporting living cells. Now, McKenney et al. show tripartite complexes dynein, and an adaptor molecule are...
An Escherichia coli dihydrofolate reductase mutant is catalytically defective, because motions in the active site are impaired.
A novel variant of the SARS-CoV-2 virus carrying a point mutation in Spike protein (D614G) has recently emerged and rapidly surpassed others prevalence. This is linkage disequilibrium with an ORF1b (P314L), making it difficult to discern functional significance D614G from population genetics alone. Here, we perform site-directed mutagenesis on wild-type human-codon-optimized introduce variant. Using multiple human cell lines, including lung epithelial cells, found that lentiviral particles...
Cryo-FIB/SEM combined with cryo-ET has emerged from within the field of cryo-EM as method for obtaining highest resolution structural information complex biological samples in-situ in native and non-native environments. However, challenges remain conventional cryo-FIB/SEM workflows, including milling thick specimens vitrification issues, preferred orientation, low-throughput when small and/or low concentration specimens, that distribute poorly across grid squares. Here we present a general...
Abstract General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, is challenging, as most peptides do not defined structures isolation, hydrogen bonds must be made to the buried polar groups peptide backbone 1–3 . Here, inspired by natural re-engineered protein–peptide systems 4–11 , we set out design of repeating units that bind with sequences, a one-to-one correspondence between repeat protein those...
Abstract A wooden house frame consists of many different lumber pieces, but because the regularity these building blocks, structure can be designed using straightforward geometrical principles. The design multicomponent protein assemblies, in comparison, has been much more complex, largely owing to irregular shapes structures 1 . Here we describe extendable linear, curved and angled as well inter-block interactions, that conform specified geometric standards; assemblies blocks inherit their...
The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development monoclonal antibody (mAb)-based immunotherapy design universal vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 A has been previously characterized that binds to a highly conserved epitope at base hemagglutinin (HA) stem activity H3, H7, H10 viruses. Here, we report second bnAb, CR8043, which was derived from different germ-line...
Abstract A novel isolate of the SARS-CoV-2 virus carrying a point mutation in Spike protein (D614G) has recently emerged and rapidly surpassed others prevalence. This is linkage disequilibrium with an ORF1b variant (P314L), making it difficult to discern functional significance D614G from population genetics alone. Here, we perform site-directed mutagenesis introduce show that multiple cell lines, including human lung epithelial cells, up 8-fold more effective at transducing cells than...
A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical designing multi-component assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) bundle oligomers (HBs). first rigidly fuse DHRs HBs generate large library oligomeric blocks. then with cyclic, dihedral, point group symmetries these blocks using architecture guided rigid fusion new software named WORMS. X-ray crystallography...
Defense against intracellular infection has been extensively studied in vertebrate hosts, but less is known about invertebrate hosts; specifically, the transcription factors that induce defense intestinal model nematode Caenorhabditis elegans remain understudied. Two different types of pathogens naturally infect C. intestine are Orsay virus, which an RNA and microsporidia, comprise a phylum fungal pathogens. Despite their molecular differences, these common host transcriptional response...
We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors the structures identify discuss key protein features evaluate how effectively these aspects were captured in submitted predictions. While overall ability to predict three-dimensional continues impress, reproducing uncommon not previously observed experimental is still a challenge. Furthermore, instances with conformational flexibility large multimeric complexes...
Abstract Natural photosystems couple light harvesting to charge separation using a ‘special pair’ of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate photophysics special pairs independently complexities native photosynthetic proteins, as first step toward creating synthetic for new conversion technologies, we designed C 2 -symmetric proteins hold two in closely juxtaposed arrangements. X-ray crystallography...
Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are enzymes in the salvage pathway, which recycles purines to meet cellular demands. Mutations of these humans cause inflammatory immunodeficiency syndromes, but mechanisms not well understood. Prior work nematode Caenorhabditis elegans demonstrated that loss PNP ortholog PNP-1 induced an immune response called intracellular pathogen (IPR). Here, we show enzyme upstream ADAH-1 (ADA homolog) also induces IPR promotes...
Beta-turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. Beta-turn mimics, molecules replace the i + 1 2 amino acid residues of a beta-turn, envisioned act as folding nucleators by preorganizing pendant polypeptide chains, thereby lowering activation barrier beta-sheet formation. However, crucial kinetic experiments demonstrate beta-turn mimics can strong in context cooperatively protein have not been...