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
- 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, […]
- 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
- A domain of CMYA5 (RID) is a novel RYR2 regulator. RID overexpression reduced arrhythmias in CPVT disease models.
- Enzymes that form nitrogen-nitrogen bonds are employed in natural product biosynthesis and the nitrogen cycle. Piperazate synthase forms the cyclic hydrazine l-piperazic acid from l-N⁵-OH-ornithine, using heme as a cofactor. In this work, we discover sequence-related enzyme NohD that instead reacts with l-N⁵-OH-ornithine to release ammonia, and we solve its structure to 1.4 Å resolution. […]
- 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 myeloid cell […]
- 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, […]