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
- Nearly half of humanity will develop cancer in their Lifetime. Current therapies, particularly chemotherapeutic drugs, face significant challenges due to the lack of tissue-specific delivery. For example, less than 0.1% of anticancer drugs administered systemically reach the tumor site, resulting in damage to healthy tissues and leading to a wide range of side effects. An […]
- The Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an immune cell specific enzyme that regulates phosphatidylinositol-(3,4,5)-trisphosphate signaling at the plasma membrane following receptor activation. SHIP1 plays an important role in processes such as directed cell migration, endocytosis, and cortical membrane oscillations. Alterations in SHIP1 expression have been shown to perturb […]
- OBJECTIVE: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate […]
- Ryanodine receptor 1 (RYR1) is the sarcoplasmic reticulum (SR) Ca^(2+) release channel required for both skeletal muscle contraction and Ca^(2+) leak. Mutations in RYR1 cause malignant hyperthermia susceptibility (MHS) and enhanced sensitivity to heat stroke (ESHS), which can result in death due to excessive skeletal muscle thermogenesis upon exposure to volatile anesthetics or heat. Here, […]
- Voltage-gated potassium ion (K^(+)) channels perform critical roles in many physiological processes, while gain- or loss-of-function mutations lead to life-threatening pathologies. Here, we establish the high-resolution structure of a pivotal intermediate state of the Kv7.1 (KCNQ1) channel using cryogenic electron microscopy. The 3.53 Å resolution structure reveals straightened upper S1 and S2 voltage sensor helices, […]
- The budding yeast Saccharomyces cerevisiae Atg1 complex coordinates the initiation of nonselective autophagy and consists of the Atg1 kinase, Atg13 regulatory subunit, and an S-shaped scaffold formed by Atg17, Atg29, and Atg31. In contrast, the fission yeast Schizosaccharomyces pombe Atg1 complex incorporates Atg101 instead of Atg29 and Atg31 and features a rod-shaped Atg17 scaffold. The […]
- Ionizable cationic lipids are a critical component of lipid nanoparticles (LNPs), enabling the clinical success of nucleic acid therapeutics through effective encapsulation, delivery, and release. As the field accelerates beyond first-generation RNA medicines, the rational design of next-generation ionizable lipids has become a key area of research. In this review, we outline key design principles […]
- PLCγ enzymes are key components of intracellular signal transduction processes and are involved in disease development, including immune dysregulation, specific cancer types, and neurodegeneration. Although recognised as important targets for intervention, validated pharmacological tools are lacking. Here, we demonstrate that inhibitory nucleotides bind directly to an allosteric site at the interface between the PLC-core and […]
- Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM dependent […]
- The Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an immune cell specific enzyme that regulates phosphatidylinositol-(3,4,5)-trisphosphate signaling at the plasma membrane following receptor activation. SHIP1 plays an important role in processes such as directed cell migration, endocytosis, and cortical membrane oscillations. Alterations in SHIP1 expression have been shown to perturb […]
- The transfection potency and biological fate of gene-loaded lipid nanoparticles (LNPs) are often determined by their morphological and physicochemical properties. Cryogenic-electron microscopy (cryo-EM) remains the most effective tool to analyze LNP morphology and internal structures in their native state, but analysis of cryo-EM micrographs is time-consuming and inefficient due to the diversity in size, shape, […]
- The class I phosphoinositide 3-kinase pathway (PI3K) is a master regulator of cellular growth, and plays essential roles in controlling immune cell function, metabolism, chemotaxis and proliferation. Activation of class I PI3Ks generates the signalling lipid PIP(3) that activates multiple pro-growth signalling pathways. Class I PI3Ks can be activated by multiple plasma membrane stimuli, including […]
- Plasminogen activator inhibitor-1 (PAI-1) deficiency is a rare disorder that causes moderate to severe bleeding and cardiac fibrosis, caused by mutation in the SERPINE-1 gene and no detectable circulating PAI-1 protein. There are currently no therapies that can effectively replace PAI-1 because the protein has a short half-life. An alternative approach to using recombinant protein […]
- Mitochondrial dysfunction is considered to drive the development of hypertrophic cardiomyopathy (HCM). In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that could alter the L-type Ca^(2+) channel's regulation of mitochondrial energetics. We confirmed that 3 of the 4 variant peptides bound with high affinity to the beta […]
- MilM from mildiomycin biosynthesis is an oxygen-, pyridoxal phosphate-dependent arginine hydroxylaseMildiomycin, a potent antifungal, is biosynthesized through a complex pathway involving the enzyme MilM. This study reassigns MilM as an oxygen (O(2))-, pyridoxal phosphate-dependent hydroxylase that hydroxylates the l-arginine-derived side chain of mildiomycin at the C4 position. This activity is conserved with the homologs MppP from enduracididine biosynthesis and RohP from azomycin biosynthesis. We found […]
- CONCLUSIONS: CVD risk in females with OA is underestimated by the FRS, an algorithm often used in clinical settings. While increased systemic inflammation, a potential intervention target, contributes to the OA-CVD link in females, there remains still unexplained increased CVD risk in OA.
- Bacteriocin peptides are weapons of inter-bacterial warfare and belong to the larger group of antimicrobial peptides (AMPs), which are frequently proposed as alternatives to antibiotics. Many AMPs kill by destroying the target's cytoplasmic membrane using short-lived membrane perturbations. Contrastingly, protein toxins form large pores by stably assembling in the target membrane. Here we describe an […]
- [This corrects the article DOI: 10.1371/journal.pone.0299894.].
- Detailed characterization of the size, mass, payload, and structure of suspended mRNA-lipid nanoparticles (LNPs) is necessary to improve our understanding of how these heterogeneous properties influence therapeutic efficacy and potency. Methods currently in use face limitations in reporting ensemble-average particle properties or requiring dedicated home-built microscopes that are beyond the reach of nanoparticle developers. In […]
- The nonstructural protein 1 (NS1) of influenza A virus performs a broad variety of proviral activities in the infected cell, primarily mediating evasion from the host innate immune response by being the main viral interferon antagonist. However, there are several interactions whose biological relevance remains obscure, such as the ability of NS1 to bind and […]