The Lyme disease agent Borrelia burgdorferi belongs to a class of metabolically compromised bacteria that cannot survive without host-derived lipids. Survival of the agent in tick and vertebrate hosts requires substantial nutrient acquisition and potential cell envelope remodeling. While prior studies identified cholesterol, cholesterol glycolipids, and phosphatidylcholines as membrane lipids in B. burgdorferi, the identity […]
A screen for adherens junction proteins regulating collective cell migration and testis morphogenesis reveals important roles for the Rab GAP RN-tre and the kinase Par-1
Animal tissues have diverse architectures and cell behaviors across the epithelial-mesenchymal spectrum. Cell adhesion mediated by classical cadherins is foundational. Cadherins nucleate complexes of dozens of proteins connecting junctions to the cytoskeleton and signaling downstream. Many junctional proteins are well-studied in epithelia, but less is known about roles during mesenchymal migration. The nascent myotubes of […]
A membrane-permeable small molecule biosensor accesses intractable cells and animals without genetic manipulation
Fluorescent biosensors have proven valuable for revealing the spatio-temporal dynamics of protein conformation in live cells and animals. The great majority of biosensors are genetically encoded, but genetic encoding is difficult or impossible to apply in many cases, including cells or animals with poorly understood genomes, no DNA, or sensitive to manipulation. Using biosensors without […]
Temperature-Dependent Rotamer Population Shifts Govern Tryptophan Fluorescence in Proteins
Intrinsic tryptophan fluorescence is widely used as a sensitive reporter of protein conformational dynamics, yet the molecular origin of its temperature-dependent modulation remains unclear. Here we investigate the conformational dynamics of Trp134 in bovine serum albumin (BSA) using molecular dynamics (MD) simulations, free-energy calculations based on umbrella sampling and WHAM, quantum mechanical (QM) calculations, and […]
A lipid compendium of a metabolically compromised bacterium provides insights into lipid acquisition, biosynthesis, and metabolism
The Lyme disease agent Borrelia burgdorferi belongs to a class of metabolically compromised bacteria that cannot survive without host-derived lipids. Survival of the agent in tick and vertebrate hosts requires substantial nutrient acquisition and potential cell envelope remodeling. While prior studies identified cholesterol, cholesterol glycolipids, and phosphatidylcholines as membrane lipids in B. burgdorferi, the identity […]
AE-PocketMiner Uses Attention to Simultaneously Predict Cryptic Pockets and Their Allosteric Coupling
Finding and targeting cryptic pockets could dramatically expand the druggable proteome. However, discovering these sites remains challenging since they are only open a fraction of the time. It is also difficult to predict the functional relevance of a cryptic site as this often requires insight into allostery. Here we introduce attention enabled (AE-)PocketMiner, an artificial […]
Unconventional biocatalytic strategies orchestrate synthesis of the nucleoside analog sinefungin
Sinefungin is a potent nucleoside antimetabolite of S-adenosylmethionine (SAM), yet its biosynthesis has remained unclear for decades. Here we detail the identification and characterization of the complete sinefungin biosynthetic gene cluster (BGC) from Streptomyces incarnatus NRRL 8089. In vitro and in vivo analyses demonstrate that the defining carbon-carbon (C-C) bond is formed not by the […]
Convergent gene erosion in the chemical defensome of marine mammals
To preserve homeostasis in the face of continual chemical insult, animals evolved dedicated molecular systems that detect, detoxify, and eliminate foreign compounds. Collectively, these enzymes, transporters, and regulatory pathways constitute the chemical defensome. In cetaceans, the loss of two key nuclear receptors (NR1I2/PXR and NR1I3/CAR) suggests a profound rearrangement of the chemical defense systems. Therefore, […]
The origin and evolution of archaeal Borg extrachromosomal elements
Borgs are giant linear extrachromosomal elements (ECEs) of methane-oxidizing Methanoperedens archaea whose evolutionary origin and ecosystem distribution remain unknown. Here we detected 240 Borgs in diverse saline, soil, and freshwater ecosystems. 27 encode methyl-coenzyme M reductases central to methane metabolism, eight have full rRNA operons related to those of Methanoperedens, and some contain up to […]
Ribo-seq reveals IsrR-mediated translational repression of SAOUHSC_02924 (gabT) during iron limitation in Staphylococcus aureus
Iron is essential for bacterial growth but can be toxic in excess. To maintain iron homeostasis, bacteria employ regulatory mechanisms, including small RNAs (sRNAs). In Staphylococcus aureus, we identified the sRNA IsrR as a critical mediator of the iron-sparing response, enabling bacterial fitness in iron-limited environments such as those encountered during host infection. Here, we […]
Evolutionary rate correlations reveal long-term co-evolutionary interactions in Drosophila melanogaster
Co-evolution between genes can occur for a variety of reasons, including co-expression of genes, epistatic interactions between them, physical interactions of gene products and many others. Co-evolutionary partners of a gene are therefore of great interest in identifying potential factors that contribute to any phenotype of interest. State-of-the-art approaches to detect these interactions use correlations […]
Morphology of petiole bending, senescence, epinasty, along with necrotic scarring in tomato leaves infiltrated with virulent Ralstonia pseudosolanacearum
Ralstonia pseudosolanacearum (Rps) belongs to the Ralstonia solanacearum species complex (RSSC). It is a vascular pathogen that causes lethal bacterial wilt disease in many plants, including tomato and eggplant. In this study, we infiltrated tomato leaves with the phytopathogenic bacterium at 109 CFU/mL and observed the development of necrotic scars in the infiltrated area at […]