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A light-activated RNA labeling method was developed to determine spatial organization of a transcriptome and found that ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial membrane.
Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles, respectively.
A crystal structure of prokaryotic pentameric ligand-gated ion channel ELIC reveals a lipid-binding site at the interface between subunits that is shaped by a flexible helix important for channel desensitization upon lipid binding.
Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain
Structural characterization of the amino-acid-modifying radical halogenase BesD and identification of new members of this protein family provides insight into the enzymatic mechanism and enables biocatalytic production of halogenated amino acids.
A 2H and 13C tracing strategy was used for efficient determination of glycolytic thermodynamics, revealing near-equilibrium glycolytic steps enabling rapid flux adaptation and, in Clostridium cellulolyticum, enhanced ATP yield.
KAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase activity.
Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty acids.
The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological dynamics.
Single-molecule analysis revealed that the velocity and force generation of the mammalian dynein–dynactin complex is regulated by activating adaptors and tail–tail interactions between two dyneins.
An in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in vivo.
A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC recycling.
Via its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon growth.
The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent dioxygenase.
A light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian cells.
Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.
Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of sepsis.
The iron chaperone poly(rC)-binding protein 1 (PCBP1) coordinates ferrous iron via its KH3 domain and, together with BolA2 and glutathione, forms a complex that is required for the assembly of [2Fe–2S] clusters on the cytosolic BolA2–Glrx3 chaperone.
Split Cpf1 pairs are identified to enable chemical- and light-induced genome editing via dimerization. Another pair of split Cpf1 can be used to activate gene expression with high efficiency in cells and in mice.
Small molecule or light-inducible gene circuits in Escherichia coli enable asymmetric cell pole localization of diguanylate phosphodiesterase and facilitate asymmetric cell division regulated by c-di-GMP-responsive transcription factors.