Journal of Molecular Biology

To date, the most detailed structural characterization of septins has been undertaken on those from opisthokonts, where heterooligomeric complexes polymerize end-to-end into filaments stabilized by alternating G- and NC-interfaces. These filaments are involved in a wide range of essential intracellular processes involving membranes, cytoskeletal components and other binding partners. Their centra…

Tyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes 3'- and 5'-phosphodiester linked DNA-adducts, including Topoisomerase I- and II-DNA covalent complexes (Topo1cc and Topo2cc). Utilizing the model organism Saccharomyces cerevisiae, which only expresses Tdp1 and does not contain TDP2 orthologs or activity, we investigated the conditions under which Tdp1 processes Topo2(peptide)cc in cells and exami…

The acquisition of vitamin B₁₂ and related cobamides is a key determinant for the fitness of Bacteroidota in the gut. Depending on the species, this uptake process relies on one to four transport systems centred on conserved core outer membrane (OM) complexes composed of the TonB-dependent transporter BtuB and the surface-exposed lipoprotein BtuG. Additionally, the surface-exposed lipo…

Preparation of high-quality nucleosomal DNA substrates in milligram quantities remains a major bottleneck for mechanistic studies of chromatin-associated processes. Here, we present an optimized large-scale PCR workflow that enables rapid, low-cost production of diverse nucleosomal DNAs suitable for biochemical assays and high-resolution cryo-EM. Systematic optimization of amplification condition…

I am currently the Choh-Ming Li Professor of Life Sciences at the School of Life Sciences (SLS) in The Chinese University of Hong Kong (CUHK). I obtained my Ph.D. in Plant Molecular Biology from Simon Fraser University in 1996 under the supervision of Dr. Allison Kermode, and then postdoc training in Plant Cell Biology at Washington State University in 1996-2000 under the supervision of Dr. John …

RNA G-quadruplexes (rG4s) are remarkably stable secondary structures with critical regulatory roles in gene expression, RNA metabolism, and telomere maintenance. However, their behavior within cells remains controversial, partly due to challenges in detecting rG4s in complex environments. Here, we use solution NMR spectroscopy to investigate how condensates formed by the low-complexity and RGG do…

• Mutation-dependent ErbB2 activation leads to accelerated ErbB2 diffusion. • EGF/EGFR-induced ErbB2 activation results in restricted lateral diffusion of ErbB2. • Cancer-associated ErbB2 mutations lead to dimerization without phosphorylation. The purpose of this study was to characterize three recurrent, cancer-associated missense mutations in ErbB2, R143Q, R678Q, and V842I, located in the extra…

To facilitate both disease research and personalised medicine, there is an urgent need for accessible, structured data models describing the molecular basis of genetically determined disease. Gene2Phenotype is a database of expert-curated monogenic gene-disease associations which was established in 2012 to enable efficient prioritisation of likely diagnostic genomic variants. Initially focused on…

G protein-coupled receptors (GPCRs) represent one of the most important drug target families, yet comprehensive and standardized GPCR-ligand interaction data remain fragmented across multiple resources. Here, we present GLASS2, a substantially expanded and methodologically enhanced database of GPCR-ligand associations. By integrating data from major pharmacological databases with a large language…

Structured Tandem Repeat Proteins (STRPs) are a subset of repeat proteins characterized by recurring structural motifs, even in cases where sequence similarity between repeats is very low. Despite substantial sequence variability, STRPs preserve conserved secondary-structure elements that underpin a wide range of biological functions. Although millions of protein structures are now publicly avail…