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Optovin is a small molecule that renders zebrafish embryos responsive to light through generation of singlet oxygen and activation of the TrpA1b channel, providing a new tool for optogenetics.
Structural analyses reveal that CopA and CupA share a binuclear Cu(I) ion binding motif and that copper is trafficked from a low-affinity site on CupA to a high-affinity site in CopA, making CupA the first membrane-bound copper chaperone important in copper resistance.
A new protein engineering approach inserts metal-coordination motifs to stabilize natural protein interfaces while other favorable contacts are removed, yielding metal-inducible protein-protein interactions that have allowed the study of a self-assembling protein cage and the chemical labeling of its interior.
π-stacking interactions unique between residues of PUMA and Bcl-xL, which lead to the unfolding of Bcl-xL via an allosteric mechanism, are required to disrupt p53–Bcl-xL interaction and induce apoptosis. This is the first example of regulated protein unfolding for signal transmission.
Methylation of lysine residues regulates chromatin function in part by recruiting readers to these marks. UNC1215, a selective antagonist of the methyllysine reader L3MBTL3 with a polyvalent mode of interaction, reveals BCLAF1 as a methyllysine-dependent interaction partner for L3MBTL3.
Bioymifi, a small-molecule death receptor 5 (DR5) agonist, induces selective cancer cell apoptosis as a single agent or in synergy with small-molecule Smac mimetics.
Cholic acid and 24(S),25-epoxycholesterol are endogenous midbrain LXR ligands that are neurogenic for red nucleus or dopaminergic neurons, respectively.
N6-Threonylcarbamoyladenosine (t6A), a modified nucleotide found in certain tRNAs, has an essential role in translational fidelity. New analytical data reveal that t6A adopts a cyclic form (ct6A) in cells and has led to the identification of the enzymes that convert t6A to ct6A.
Quantification of cytosolic glutathione redox potential leads to the discovery that the ABC-C transporter Ycf1 rapidly transports oxidized glutathione (GSSG) into vacuoles and whole-cell GSSG should not be used as a proxy for cytosolic GSSG.
An allosteric activator of Hsp70 mimics Hip and reduces neurotoxicity in a model for spinobulbar muscular atrophy by promoting ubiquitination and degradation of oligomeric polyglutamine-containing clients.
Allosteric conformations and proteolytic activities of each subunit of the trimeric E. coli DegS protease share a cooperatively coupled energy landscape that allows regulation via the binding of substrate and OMP peptides.
Maintaining energy homeostasis requires complex feedback across organs that is difficult to study in isolated systems. New research uses whole-organism screening to identify key regulators of fasting metabolism in zebrafish, including ligands for the mitochondrial transporter protein TSPO.
Stabilization of ubiquitin's β1-β2 region by computational design and phage display, targeting both buried and surface residues, yields a ubiquitin variant that specifically inhibits the deubiquitinase USP7 in vitro and in cells.
The human genome contains stretches of DNA sequence with unknown function. Peptidomics coupled to RNA-Seq now reveals a class of short open reading frames in human genomes that are translated into small peptides.
Medium-sized ring structures can provide unique entry points into natural product–like chemical space but are synthetically challenging to access. A biologically inspired method eases these challenges, employing a dearomatization-rearomatization sequence to form a diverse library of rings from tailored bicyclic compounds.
Equilibrium isomerization of retinol is a new activity now attributable to DES1. 11-cis-retinol synthesized by DES1 in Müller cells of the retina can be converted to the visual chromophore for regenerating opsin pigment in cone photoreceptors.
Acanthaporin is identified as a pore-forming protein from the infectious Acanthamoeba culbertsoni with a previously unknown structure. The newly identified structure includes a pH-dependent histidine switch that controls partitioning between the inactive dimer and the active monomer, which assembles into larger species to cause toxicity.
Src family kinase mutants, with altered regulatory domain interactions, were profiled with a photodependent crosslinking strategy to reveal conformation-specific ATP-competitive inhibitors that affect intermolecular binding interactions.
OGT modifies numerous proteins with O-GlcNAc, but the mechanism for this reaction has been difficult to define. Ternary crystal structures and activity assays with substrate analogs now provide evidence that the α-phosphate of the donor substrate is the catalytic base.
The creation and application of engineered constructs specific for one of two IL-4 coreceptors explain how immune signaling is limited by coreceptor concentration and establish specific roles for type II receptor–specific signaling in dendritic cell differentiation.