A5054514648- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Nuclear Structure and Function
- Peptidase Inhibition and Analysis
- Bacteriophages and microbial interactions
- Crystallization and Solubility Studies
- Catalytic Processes in Materials Science
- RNA Interference and Gene Delivery
- Mesoporous Materials and Catalysis
- Virology and Viral Diseases
- Animal Virus Infections Studies
- Radioactive element chemistry and processing
- Viral Infections and Vectors
- Influenza Virus Research Studies
The University of Texas at Austin
2025
St. Jude Children's Research Hospital
2021-2023
Tri-Institutional PhD Program in Chemical Biology
2018-2022
Cornell University
2018-2022
California Institute of Technology
2015-2022
Weill Cornell Medicine
2018-2022
National Institute of Allergy and Infectious Diseases
2015-2019
National Institutes of Health
2015-2019
Antibodies to the prefusion conformation of RSV F glycoprotein neutralize natural infection.
Blueprint for a macromolecular machine Nuclear pore complexes (NPCs) consist of around 1000 protein subunits, are embedded in the membrane that surrounds nucleus, and regulate transport between nucleus cytoplasm. Although overall shape NPCs is known, details this complex have been obscure. Now, Lin et al. reconstituted components, determined interactions them, fitted them into tomographic reconstruction. Kosinski provided an architectural map inner ring pore. Science , issue pp....
INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion inner outer membranes, pore complexes (NPCs) sole bidirectional gateways for nucleocytoplasmic transport. ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies ~34 different proteins, collectively termed nucleoporins. symmetric core...
Abstract In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the mechanism derives principally from studies on bacterial systems 1 . Although key features are conserved across evolution 2 , eukaryotes achieve higher-fidelity mRNA than bacteria 3 human, changes in fidelity linked to ageing and disease represent a potential point therapeutic intervention both viral cancer treatment...
Building a gate to the nucleus Nuclear pore complexes form gateway between cytoplasm and (see Perspective by Ullman Powers). Stuwe et al. combined structural, biochemical, functional analyses elucidate architecture of six-protein complex that makes up inner ring fungal nuclear pore. This includes central trimeric homologous Nup62 found in metazoans is incorporated into inner-ring complex. Chug report structure metazoan Neither study supports model which can dilate constrict. Instead they...
Peptide-chain elongation during protein synthesis entails sequential aminoacyl-tRNA selection and translocation reactions that proceed rapidly (2-20 per second) with a low error rate (around 10-3 to 10-5 at each step) over thousands of cycles1. The cadence fidelity ribosome transit through mRNA templates in discrete codon increments is paradigm for movement biological systems must hold diverse tRNA substrates across domains life. Here we use single-molecule fluorescence methods guide the...
Translocation moves the tRNA2⋅mRNA module directionally through ribosome during elongation phase of protein synthesis. Although translocation is known to entail large conformational changes within both and tRNA substrates, orchestrated events that ensure speed fidelity this critical aspect synthesis mechanism have not been fully elucidated. Here, we present three high-resolution structures intermediates on mammalian where, in contrast bacteria, ribosomal complexes containing translocase eEF2...
Rapid and accurate mRNA translation requires efficient codon-dependent delivery of the correct aminoacyl-tRNA (aa-tRNA) to ribosomal A site. In mammals, this fidelity-determining reaction is facilitated by GTPase elongation factor-1 alpha (eEF1A), which escorts aa-tRNA as an eEF1A(GTP)-aa-tRNA ternary complex into ribosome. The structurally unrelated cyclic peptides didemnin B ternatin-4 bind inhibit but have different effects on protein synthesis in vitro vivo. Here, we employ...
Respiratory syncytial virus (RSV) subtypes, A and B, co-circulate in annual epidemics alternate dominance. We have shown that a subtype RSV fusion (F) glycoprotein, stabilized its prefusion conformation by DS-Cav1 mutations, is promising RSV-vaccine immunogen, capable of boosting RSV-neutralizing titers healthy adults. In both humans vaccine-tested animals, neutralizing elicited this immunogen were ~ 2- to 3-fold higher against the homologous than heterologous B virus.To understand molecular...
Significance The increase in multidrug-resistant bacteria highlights the urgent need for compounds with novel target sites that can be developed as antibiotics. argyrins represent a family of naturally produced octapeptides display promising activity against Pseudomonas aeruginosa by inhibiting protein synthesis. Our structural and kinetic analyses reveal inhibit synthesis interacting with, trapping, translation elongation factor G (EF-G) on ribosome, analogous to reported previously...
Translocation of messenger RNA (mRNA) and transfer (tRNA) substrates through the ribosome during protein synthesis, an exemplar directional molecular movement in biology, entails a complex interplay conformational, compositional, chemical changes. The determinants early translocation steps have been investigated rigorously. However, elements enabling to complete reset for subsequent synthesis reactions remain poorly understood. Here, we combined simulations with single-molecule fluorescence...
Abstract The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating NPC symmetric core architecture, asymmetrically decorated cytoplasmic face, essential mRNA export and a hotspot nucleoporin-associated diseases, has remained elusive. Here, we report composite structure of entire human face obtained by combining biochemical reconstitution, crystal determination, docking into cryo-electron tomographic...
Abstract Rapid and accurate mRNA translation requires efficient codon-dependent delivery of the correct aminoacyl-tRNA (aa-tRNA) to ribosomal A site. In mammals, this fidelity-determining reaction is facilitated by GTPase elongation factor-1 alpha (eEF1A), which escorts aa-tRNA as an eEF1A(GTP)-aa-tRNA ternary complex into ribosome. Two structurally unrelated cyclic peptides didemnin B ternatin-4 bind inhibit translation. Here, we employ single-molecule fluorescence imaging cryogenic...