Browse Articles

A repurposed AMP binding domain reveals mitochondrial protein AMPylation as a regulator of cellular metabolism

Abstract Protein AMPylation, the covalent addition of adenosine monophosphate (AMP) to protein substrates, has been known as a post translational modification for over 50 years. Research in this field is largely underdeveloped due to the lack of tools that enable the systematic identification of AMPylated substrates. Here, we address this gap by developing an enrichment technique to isolate and study AMPylated proteins using a nucleotide-binding protein, hinT. Cryo-EM reconstruction of an AMPylated protein bound to hinT provides a structural basis for AMP selectivity. Using structure guided mutagenesis, we optimize enrichment to identify novel substrates of the evolutionarily conserved AMPylase, Selenoprotein O. We show that mammalian Selenoprotein O regulates metabolic flux through AMPylation of key mitochondrial proteins including glutamate dehydrogenase and pyruvate dehydrogenase. Our findings highlight the broader significance of AMPylation, an emerging post translational modification with critical roles in signal transduction and disease pathology. Furthermore, we establish a powerful enrichment platform for the discovery of novel AMPylated proteins to study the mechanisms and significance of protein AMPylation in cellular function.

Molecular landscape, subtypes, and therapeutic vulnerabilities of central nervous system solitary fibrous tumors

The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm

Determining kinetics of H2O2 evolution from photoelectrochemical water oxidation

Atomically precise gold nanocluster boosting selective hydrogenation of nitroarene by H2 in water

Anomalous photoelectrochemical etching of undoped semiconductor surfaces

LncRNA HSCHARME is altered in human cardiomyopathies and promotes stem cell-derived cardiomyogenesis via splicing regulation

Global decarbonization corresponding with unseasonal land cover change

Probing weak chemical interactions of metal surface atoms with CO-terminated AFM tips identifies molecular adsorption sites

Abstract Metal surfaces play a key role in on-surface synthesis as they provide a two-dimensional catalytic reaction environment that stimulates activation, diffusion, and coupling of molecular reactants. Fundamental understanding of the interactions between surface atoms and reactants is very limited but would enable controlling on-surface reaction processes for designing functional nanomaterials. Here, we measure chemical interactions between CO-terminated tips and Cu(111), Ag(111), and Au(111) surface atoms in all spatial directions with picometer resolution via low temperature atomic force microscopy. This allows a site-specific quantification of the weak chemical interactions of densely packed metal surface atoms and provides a picture of the potential energy landscape experienced by adsorbed reactants. Accompanying density functional theory calculations and the crystal orbital overlap population method reveal small covalent binding contributions from orbital overlap of the corresponding p- and d-states of the CO tip and the metal surface atoms as the cause for the site-specific interactions. Accessing such small covalent bonding contributions in the background of the dispersion-dominated interaction enables revealing insights into the nature of chemical bond formation with metal surface atoms and a reliable determination of molecular adsorption sites. The latter can serve both as a starting point and as a direct comparison with theoretical studies.

Molecular engineering of melanin for enhanced biological γ-ray protection

Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking

Structure-guided engineering of type I-F CASTs for targeted gene insertion in human cells

Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas

Abstract Placental biopsy in early pregnancy is widely used in prenatal genetic diagnostics as a surrogate for fetal tissue. Confined placental chromosomal mosaicism is a well-documented phenomenon causing genetic discrepancies between the fetus and placenta. Although comprehensive sequencing methods are becoming popular for prenatal screening of monogenic disorders, knowledge of concordance between the fetus and early placenta at the sequence level remains limited. By deep genome sequencing, we have mapped the mutational landscape across multiple sites and stages of placental development. We have revealed wide-spread mutations, with distinct clusters of postzygotic non-fetal small sequence variants, indicating extensive clonal evolution in all early placental biopsies, including first-trimester chorionic villus samples. Our study illuminates spatial and temporal genetic heterogeneity of the developing placenta. While most clonal sequence variants in placental biopsies exhibit low variant allele frequency, their presence underscores the need for caution when using placental tissue as a fetal proxy for diagnostics. These findings highlight the importance of confirmatory testing using AF in cases where placental mosaicism is suspected to avoid misinterpretation and unnecessary interventions.

Evolutionary age correlates with range size across plants and animals

Abstract More than 40 thousand species of plants and animals are facing extinction worldwide. Range size is one of the strongest determinants of extinction risk, but the causes underlying the wide variation in natural range sizes remain poorly understood. Here, we investigate how species’ age is related to present-day range size for over 26,000 species of mammals, birds, reptiles, amphibians, reef fishes, and plants. We show that, on average, older species have larger ranges across all groups except for marine mammals, but the strength of the age-range size relationship depends on taxonomic scale. Furthermore, while our results confirm the well-established pattern of smaller range sizes for species restricted to islands (compared to mainland) or with limited dispersal abilities (compared to good dispersers), we show that the correlation between species age and range size is stronger in these groups, suggesting that island dynamics and dispersal ability modulate this relationship. Our study reveals that species with small ranges, and thus increased extinction risk, tend to be restricted to islands, are poor dispersers, or have recently evolved.

Mesothelin-directed protein-drug conjugates for mesothelin-low solid tumor therapy

Reversible biobased adhesives enable closed-loop engineered composites

Wide temperature range adaptable electric field driven binder for advanced lithium-sulfur batteries

Towards generalist foundation model for radiology by leveraging web-scale 2D&3D medical data

Mechanosensitive channel engineering: A study on the mixing and matching of YnaI and MscS sensor paddles and pores

Abstract Osmotically varying environments are challenging for bacterial cells. Sudden drops in osmolytes cause an increased membrane tension and rupture the cells in the absence of protective mechanisms. One family of protective proteins are mechanosensitive channels of small conductance that open in response to membrane tension. Although these channels have a common architecture, they vary widely in the number of transmembrane helices, conductivity, and gating characteristics. Although there are various structures of channels in the open and closed state, the underlying common principles of the gating mechanism remain poorly understood. Here we show that YnaI opens by radial relocation of the transmembrane sensor paddles together with a shortening of the pore, which contrasts the prototypic smaller MscS. A chimera of both channels with the YnaI sensor paddles and the pore containing C-terminal part of MscS is functional and has the tension response of the paddle donor. Our research shows that elements with different structural opening mechanisms can be mixed and matched within one channel as long as they support the common area expansion on the periplasmic side.

Neural and behavioral reinstatement jointly reflect retrieval of narrative events