- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Advanced Electron Microscopy Techniques and Applications
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Photosynthetic Processes and Mechanisms
MRC Laboratory of Molecular Biology
2020-2024
MRC Laboratory for Molecular Cell Biology
2022
Yale University
2014-2016
Abstract Background Protein transporters translocate hydrophilic segments of polypeptide across hydrophobic cell membranes. Two protein are ubiquitous and date back to the last universal common ancestor: SecY YidC. consists two pseudosymmetric halves, which together form a membrane-spanning protein-conducting channel. YidC is an asymmetric molecule with groove that partially spans membrane. Although both mediate insertion membrane proteins short translocated domains, only transports...
The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can...
The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can...
Genome engineering technologies now enable precise manipulation of organism genotype, but can be limited in scalability by their design requirements. Here we describe Merlin (http://merlincad.org), an open-source web-based tool to assist biologists designing experiments using multiplex automated genome (MAGE). provides methods generate pools single-stranded DNA oligonucleotides (oligos) for MAGE performing free energy calculation and BLAST scoring on a sliding window spanning the targeted...
The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-EM structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain conformation...
The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-EM structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain conformation...
Abstract Cells use transporters to move protein across membranes, but the origins of most ancient are unknown. Here, we analyse ubiquitous protein-conducting channel SecY. Features conserved by its two duplicated halves suggest that their common ancestor was an antiparallel homodimeric channel. Structural searches with SecY’s detect exceptional similarity only other transporter, YidC. Their shared fold comprises a three-helix bundle interrupted helical hairpin. In YidC this hairpin is...
Abstract The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-EM structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain...