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
- 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 […]
- 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 […]
- Sensory induction of mecA expression plays a pivotal role in mediating broad-spectrum β-lactam resistance (BBR) of MRSA. In contemporary MRSA isolates, sensory induction of BBR originates at the membrane-localized BlaR1, which, upon detection of β-lactam drugs, triggers a signal transduction cascade that promotes mecA induction. We hereby showed that phosphorylation of BlaR1, mediated through the […]
- Self-amplifying RNA (saRNA)-lipid nanoparticle (LNP) therapeutics represent a transformative advance in nucleic acid medicine, enabling prolonged protein expression at significantly lower doses compared to traditional mRNA-LNP systems. However, their broader clinical translation is hindered by pronounced innate immune activation elicited by saRNA replication intermediates and LNP components. To address this challenge, we investigated lipid-derivatized prodrugs […]
- Exclusive to Firmicutes, endospore formation is a complex process that results in the release of a mature spore after the mother cell lyses. The spore is protected by multiple layers, including inner and outer spore membranes (IsM and OsM), both originating from the mother cell's inner membrane (IM). While well understood in monoderm bacteria like […]
- The SARS-CoV-2 nucleocapsid (N) protein is essential for viral RNA packaging, replication, and immune modulation. Despite its central role, the mechanistic contributions of its individual domains, the N-terminal domain (NTD), C-terminal domain (CTD), and the intrinsically flexible linker (LINK), remain poorly defined, largely due to the protein's structural complexity. In this study, we developed a […]
- The gating of HCN channels is regulated by both voltage and the binding of cyclic nucleotides to their intracellular domain. However, the molecular determinants underlying this regulation by cyclic nucleotide binding remain unclear and controversial. Here, we combine theoretical and experimental approaches to investigate the binding process in the HCN2 channel. First, molecular dynamics simulations […]
- Metastatic progression in aggressive breast cancer (BC) depends on a tightly controlled vesicular recycling network regulated by RAB11, a small guanosine triphosphate enzyme (GTPase). In a cohort of more than 1,000 patients with BC, we identified SH3BP5L as the most highly expressed guanine nucleotide exchange factor (GEF) for RAB11A. High SH3BP5L expression marked an advanced […]
- Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as […]
- Plasminogen activator inhibitor 1 (PAI-1) is an inhibitor of fibrinolysis, thereby promoting blood clot stabilization. PAI-1 contributes to thrombosis, diet-induced obesity, and age-associated diseases such as diabetes, cancer, and Alzheimer's disease. Circulating PAI-1 increases with age, contributing to the increased thrombotic risk in age-related diseases. In contrast, partial PAI-1 deficiency protects patients from cardiovascular morbidity […]
- OBJECTIVES: Chatbot-delivered treatments offer tremendous mental health benefits. This systematic review aimed at examining the effectiveness of using chatbots for improving mental health among people in Asia.
- Phosphatidylinositol 4 kinase IIIα (PI4KIIIα/PI4KA) is an essential lipid kinase that plays a critical role in regulating plasma membrane identity. PI4KA is primarily recruited to the plasma membrane through the targeted recruitment by the proteins, EFR3A and EFR3B, which bind to the PI4KA accessory proteins TTC7 (TTC7A/B) and FAM126 (FAM126A/B). Here we characterised how both […]
- Deciphering the heterogeneity of mRNA-containing lipid nanoparticles (LNPs) is essential for understanding the relationship between their microscopic properties and therapeutic function. Here, by combining alternating laser excitation (ALEX) with convex lens-induced confinement (CLiC) microscopy, we simultaneously measure size, multicolor fluorescence, mRNA payload, and Förster resonance energy transfer (FRET) of individual suspended LNPs containing labeled lipid […]
- Malignant Hyperthermia Susceptibility (MHS) is a pharmacogenetic disorder triggered by volatile anesthetics and muscle relaxants, leading to a hypermetabolic reaction in skeletal muscle that can be fatal if untreated. Diagnosis relies on an in vitro contracture test (IVCT) on muscle biopsy and/or genetic testing for pathogenic variants in the RYR1 gene, which accounts for most […]
- Mitochondrial protein import is required for maintaining organellar function¹. Perturbations in this process are associated with various physiological and disease conditions². Several stress responses, including the mitochondrial compromised protein import response (mitoCPR), combat damage caused by mitochondrial protein import defects². However, how this defect is sensed remains largely unknown. Here we reveal that the conserved […]
- Retinitis pigmentosa (RP) associated with mutations in the rhodopsin gene (RHO) is a significant cause of blindness. Here we report on the application of adenine base editing of the c.1030C>T (p.Q344X) RHO mutation linked to RP. Using a fluorescence reporter cell system, we optimized editing by exploring base editors, sgRNA, and delivery methods. Flow cytometry, […]
- Next-generation antibodies include a growing number of bispecific and multispecific antibodies that are commonly used to redirect the immune system to fight cancer. Herein, we assessed the depth and breadth of epitope coverage as a proxy for functional diversity in human immune repertoires produced by two complementary in vivo platforms utilizing a common light chain, […]