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
- 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 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 […]
- 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, […]
- 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 […]
- 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, […]
- No abstract
- Statins are the most prescribed class of drugs and inhibit a key enzyme in the cholesterol biosynthesis pathway. Many patients have reported mild to severe muscle related symptoms and a subset are at risk for rhabdomyolysis. Sequence variants in RyR1, the skeletal muscle Ryanodine Receptor, correlate with intolerance to statins, but whether RyR1 can bind […]
- The ryanodine receptor (RyR) is a critical drug target, yet dantrolene (DAN) remains the only FDA-approved inhibitor, limited by hepatotoxicity and unsuitable for chronic use. To guide improved inhibitor development, we determine high-resolution crystal structures of the RyR Repeat12 (R12) domain bound to DAN, its analog azumolene (AZU), and adenine nucleotides (AMP-PCP or ADP). DAN/AZU […]
- Staphylococci secrete amphipathic peptides known as phenol soluble modulins (PSMs) that play a variety of pathogenic roles including host cell membrane destruction, biofilm development, and the triggering of inflammatory responses. PSM export is facilitated by the essential ATP-binding cassette (ABC) transporter PmtCD, which also provides producer immunity toward the membrane-damaging PSMs. Here, we report cryo-EM […]
- Class IA phosophoinositide kinases (PI3Ks) are master regulators of growth, metabolism, and immunity. The class IA PI3Ks are a heterodimer composed of a p110 catalytic subunit and one of five possible regulatory subunits (p85α, p85β, p55γ, p55α, p50α). The regulatory subunit plays critical roles in stability, inhibition, and activation of the p110 catalytic subunit. The […]
- Phosphatidylinositol 4 kinase IIIα (PI4KIIIα/PI4KA) is an essential lipid kinase that plays a critical role in regulating plasma membrane (PM) identity. PI4KA is primarily recruited to the PM 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 characterized how both […]
- Members of the genus Pseudomonas synthesize diverse natural products that contribute to their versatility in free-living and host-associated lifestyles. Here, we characterized the in vivo functions of the nitroimidazole antibiotic azomycin in the genus Pseudomonas. We found that genes with similarity to azomycin biosynthesis genes rohPQRST are prevalent within the Pseudomonas syringae species complex and […]
- No abstract