A5081556454- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Biochemical and Structural Characterization
- Genomics and Phylogenetic Studies
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Spectroscopy and Quantum Chemical Studies
- CAR-T cell therapy research
- Photochemistry and Electron Transfer Studies
- DNA and Nucleic Acid Chemistry
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Molecular Biology Techniques and Applications
- Toxin Mechanisms and Immunotoxins
Elements Biosciences (United States)
2023
California Institute of Technology
2013-2021
Division of Chemistry
2017
National Taiwan University
2014
Abstract We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along DNA template and identifying each nucleotide within template. Nucleotide identification uses multivalent ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound clonal copies targets. These polymer–nucleotide substrates, termed avidites, decrease required concentration reporting nucleotides from micromolar nanomolar yield negligible dissociation...
Abstract During co-translational protein targeting, the signal recognition particle (SRP) binds to translating ribosome displaying sequence deliver it SRP receptor (SR) on membrane, where peptide is transferred translocon. Using electron cryo-microscopy, we have determined structure of a quaternary complex Escherichia coli ribosome, SRP–SR in ‘activated’ state and Our structure, supported by biochemical experiments, reveals that RNA adopts kinked untwisted conformation allow repositioning...
The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates co-translational targeting proteins to correct cellular membrane. During reaction, two functional ends in mediate distinct functions. Whereas tetraloop facilitates initial assembly GTPases between receptor, this GTPase complex subsequently relocalizes ∼100 Å 5′,3′-distal end RNA, conformation crucial for activation cargo handover. Here we combined biochemical, single...
Peptide–major histocompatibility complex (pMHC) multimers enable the detection, characterization, and isolation of antigen-specific T-cell subsets at single-cell level via flow cytometry fluorescence microscopy. These labeling reagents exploit a multivalent scaffold to increase avidity individually weak receptor (TCR)-pMHC interactions. Dextramers are an improvement over original streptavidin-based tetramer technology because they more multivalent, improving sensitivity for rare, low-avidity...
Significance The universally conserved signal recognition particle (SRP) delivers ∼30% of the proteome to appropriate cellular membrane. How SRP achieves efficient and selective protein targeting in eukaryotes remains elusive. Here, we show that a functional sequence on nascent polypeptide confers significant kinetic privilege ribosome-bound during recruitment receptor, thereby enabling rapid membrane SRP-dependent substrates. In addition, single-molecule spectroscopy revealed ribosome-...
Single-molecule and cryo-EM studies reveal molecular acrobatics of signal recognition particle that initiates protein translocation.
Molecular recognition features (MoRFs) provide interaction motifs in intrinsically disordered protein regions to mediate diverse cellular functions. Here we report that a MoRF element, located the linker domain of mammalian signal particle (SRP) receptor and conserved among eukaryotes, plays an essential role sensing ribosome during cotranslational targeting endoplasmic reticulum. Loss SRP (SR) largely abolishes ability activate SRP-SR assembly impairs targeting. These results demonstrate...
The signal recognition particle (SRP) delivers ~30% of the proteome to eukaryotic endoplasmic reticulum, or bacterial plasma membrane. precise mechanism by which SRP receptor, FtsY, interacts with and is regulated at target membrane remain unclear. Here, quantitative analysis FtsY-lipid interactions single-molecule resolution revealed a two-step in FtsY initially contacts via Dynamic mode, followed an SRP-induced conformational transition Stable mode that activates for downstream steps....
Abstract We present avidity sequencing - a novel chemistry that separately optimizes the process of stepping along DNA template and identifying each nucleotide within template. Nucleotide identification uses multivalent ligands on dye-labeled cores to form polymerase-polymer complexes bound clonal copies targets. These polymer-nucleotide substrates, termed avidites, decrease required concentration reporting nucleotides from micromolar nanomolar, yield negligible dissociation rates....
Abstract Signal recognition particle (SRP) is a universally conserved targeting machine that couples the synthesis of ~30% proteome to their proper membrane localization 1,2 . In eukaryotic cells, SRP recognizes translating ribosomes bearing hydrophobic signal sequences and, through interaction with receptor (SR), delivers them Sec61p translocase on endoplasmic reticulum (ER) How ensures efficient and productive initiation protein translocation at ER not well understood. Here, single...