Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus. Alexander JAN, Worrall LJ, Hu J, Vuckovic M, Satishkumar N, Poon R, Sobhanifar S, Rosell FI, Jenkins J, Chiang D, Mosimann WA, Chambers HF, Paetzel M, Chatterjee SS, Strynadka NCJ. Nature. 2023 Jan;613(7943):375–82.
Chemoproteomic identification of CO2-dependent lysine carboxylation in proteins. King DT, Zhu S, Hardie DB, Serrano-Negrón JE, Madden Z, Kolappan S, Vocadlo DJ. Nat Chem Biol. 2022 Jul;18(7):782–91.
Biochemical and structural characterization of Rab3GAP reveals insights into Rab18 nucleotide exchange activity. Fairlie GMJ, Nguyen KM, Nam SE, Shaw AL, Parson MAH, Shariati HR, Wang X, Jenkins ML, Gong M, Burke JE, Yip CK. Nat Commun. 2025 Jan 8;16(1):479.
A heme-dependent enzyme forms the hydrazine in the antibiotic negamycin. Wang M, Wei ZW, Ryan KS. Nat Chem Biol. 2025 Jul;21(7):1012–20.
The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Cullis PR, Felgner PL. Nat Rev Drug Discov. 2024 Sep;23(9):709–22.
Cryo-EM structures of ryanodine receptors and diamide insecticides reveal the mechanisms of selectivity and resistance. Lin L, Wang C, Wang W, Jiang H, Murayama T, Kobayashi T, Hadiatullah H, Chen YS, Wu S, Wang Y, Korza H, Gu Y, Zhang Y, Du J, Van Petegem F, Yuchi Z. Nat Commun. 2024 Oct 20;15(1):9056.
Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity. Bathula NV, Friesen JJ, Casmil IC, Wayne CJ, Liao S, Soriano SKV, Ho CH, Strumpel A, Blakney AK. J Control Release Off J Control Release Soc. 2024 Oct;374:28–38.
Cell envelope diversity and evolution across the bacterial tree of life. Hashimi A, Tocheva EI. Nat Microbiol. 2024 Oct;9(10):2475–87.
A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. Shapira T, Monreal IA, Dion SP, Buchholz DW, Imbiakha B, Olmstead AD, Jager M, Désilets A, Gao G, Martins M, Vandal T, Thompson CAH, Chin A, Rees WD, Steiner T, Nabi IR, Marsault E, Sahler J, Diel DG, Van de Walle GR, August A, Whittaker GR, Boudreault PL, Leduc R, Aguilar HC, Jean F. Nature. 2022 May;605(7909):340–8.
Extended List of Recent Work from ASTRID
- MR1 is a non-polymorphic, ubiquitously expressed, MHC class I-like antigen-presenting molecule that presents small-molecule metabolites to T cells. Studies have shown that MR1 plays a role in microbial infection, inflammation, and tumor immunity. The antigens it presents include metabolites of microbial and self-origin as well as small-molecule drugs and form stable complexes with MR1 that […]
- mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccines during the COVID-19 pandemic provided an unprecedented real-world evaluation of this platform, with billions of doses administered across diverse populations. In this Review, we critically examine the safety […]
- Auxiliary β1 subunits play an important role in modulating voltage-gated Na+ (NaV) channel gating, thereby influencing their voltage-dependent behavior and overall function. Here, we examine β1 modulation of human NaV1.6 channels expressed in Xenopus laevis oocytes and identify a glutamate in the extracellular S3-S4 loop of domain IV (VSDIV; E1607) as a key determinant of […]
- The armadillo repeat protein ARMH3 regulates the activity and localisation of the Golgi resident lipid kinase phosphatidylinositol 4 kinase IIIβ (PI4KB) and the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) that activates Arf1. ARMH3 localises to the trans-Golgi network (TGN) via the GTPase Arl5. We used hydrogen deuterium exchange mass spectrometry (HDX-MS) and […]
- The unambiguous identification of protein O-GlcNAcylation remains challenging because O-GlcNAc and O-GalNAc are isobaric and produce nearly indistinguishable fragmentation patterns under standard higher-energy collisional dissociation (HCD) conditions. Here, we report a chemoenzymatic strategy that enables selective detection of O-GlcNAc through enzymatic deacetylation. We show that the Cyclobacterium marinum deacetylase CmCBDA uniquely and efficiently converts beta-O-GlcNAc, […]
- No abstract
- Lipid nanoparticles (LNP) are currently the most advanced delivery platform for mRNA therapeutics. To reach extrahepatic tissues, it is beneficial to engineer LNP-mRNA systems with improved stability and prolonged blood circulation lifetimes. In previous work we have shown that LNP-mRNA systems with liposomal morphology that contain egg sphingomyelin (ESM) can exhibit longer circulation lifetimes and […]
- The direct binding of cAMP to the hyperpolarization-activated cyclic nucleotide-gated channel form 4 (HCN4) protein contributes to autonomic modulation of heart rate. Here, we determine affinity for binding of cyclic nucleotides directly to the cytosolic C-terminus of the HCN4 channel of three disease-linked mutations that are found in the C-linker of the C-terminus, which attaches […]
- The optimization of mRNA-lipid nanoparticles (mRNA-LNPs) for therapeutic applications is limited in part by the inadequate characterization of mRNA payload heterogeneity. One current challenge is accurately measuring the number of mRNA copies within individual LNPs, where the standard method of intensity-based mRNA number determination is sensitive to fluorescent dye-dye interactions and heterogeneity of mRNA labeling. […]
- Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle-wasting disease caused by aberrant activation of the DUX4 gene in skeletal muscle. Antisense oligonucleotides (ASOs) targeting DUX4 have shown therapeutic potential, but challenges related to systemic delivery and efficacy limit their clinical utility. In this study, we explored lipid nanoparticle (LNP)-mediated delivery of optimized locked nucleic acid […]
- Viral internal ribosome entry sites (IRESs) are specialized RNA structures that facilitate cap-independent translation as a strategy to usurp the host translational machinery. The Type 6 IRESs are the most streamlined mechanism to date, as they adopt a three pseudoknot RNA structure to initiate factorless translation initiation by directly recruiting the ribosome and drive translation. […]
- The availability of T-cell therapies is limited in part due to their complex and costly biomanufacturing. Genetic engineering of T cells, such as to express chimeric antigen receptor (CAR), is commonly achieved using viral vectors, that are costly to produce and add to safety concerns. Non-viral alternatives have advantages, but a major barrier is their […]
- Androgen receptor (AR) is a therapeutic target for prostate cancer. Despite effectively targeting its folded ligand-binding domain (LBD), resistance ultimately develops by mechanisms involving reactivation of AR signaling. These mechanisms include expression of constitutively active AR that lacks LBD and fueled the discovery of inhibitors that bind to AR's N-terminal intrinsically disordered transactivation domain (TAD). […]
- Base editors have emerged as powerful tools for precise genome editing, offering significant therapeutic potential. A critical challenge lies in optimizing the delivery and dosage of single-guide RNA to maximize on-target editing efficiency while minimizing off-target and bystander effects. This study investigates the impact of guide RNA dosage on in vivo editing efficiency and tissue […]
- Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is an established technique that measures the exchange rate of amide hydrogens, with this exchange rate being a surrogate for protein conformational dynamics. Advances in instrumentation, automation, and data analysis have transformed HDX-MS into a high-throughput and highly reproducible method capable of probing complex biological systems and addressing key questions […]
- The reasons why two multiprotein complexes – VPS34 complex I and VPS34 complex II – are activated by different Rab proteins are becoming clearer.
- Copper radical oxidases (CROs), which comprise Auxiliary Activity Family 5 (AA5) in the Carbohydrate-Active Enzymes (CAZy) classification, have a long history of study due to their unique catalytic mechanism and biotechnological applications. The majority of mechanistic and structural insights into CRO function have been obtained from studies on the galactose 6-oxidase from the fungal phytopathogen […]
- In previous work, we have shown that negatively charged gold nanoparticles (GNPs) can be coencapsulated into lipid nanoparticles (LNPs) containing ionizable cationic lipids using a process similar to that employed for encapsulating nucleic acids. These systems can subsequently be used to encapsulate weak base drugs such as doxorubicin (DOX), enabling triggered release systems employing laser […]
- The nitro group is an important functional group found in the nitroimidazoles, antibiotic therapeutics for anaerobic pathogens. In the biosynthetic pathway to the nitroimidazole antibiotic azomycin, a nitro-forming enzyme RohS-a member of the heme-oxygenase-like dimetal/domain-containing oxidase/oxygenase (HDO) family-catalyzes a six-electron oxidation of 2-aminoimidazole to 2-nitroimidazole. Here, we present the 2.20 Å resolution crystal structure of […]
- Many voltage-gated sodium channel-targeting animal peptide toxins are renowned for their potency and selectivity against insects. Understanding why these toxins selectively target insect sodium channels over their mammalian counterparts is crucial for developing safer and more effective pest control agents. Here, we present the cryoelectron microscopy (cryo-EM) structures of the insect sodium channel Na(v)PaS bound […]