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Extended synaptotagmins (E-Syts) mediate the tethering of endoplasmic reticulum and the plasma membrane. High-resolution optical tweezers revealed the energetics, kinetics and force generation of membrane binding by a single E-Syt molecule.
RNA acetyltransferase TmcA functions as a lysine 2-hydroxyisobutyryltransferase to regulate bacterial transcription in response to acid stress in prokaryotes.
Nutrient stress induces ATF4 expression via translation reinitiation, which involves eIF3 retainment on the elongating ribosome. This translational reprogramming is mediated by stress-induced removal of the O-GlcNAc modification from eIF3a.
Photoaffinity analogs of a family of glycosylated macrolides, apoptolidins, revealed the F1 subcomplex of mitochondrial ATP synthase as the target. Cryo-EM analysis of the apoptolidin–ATP synthase complex enabled identification of resistance mutations.
BURP domains within lyciumin precursor peptides serve as autocatalytic peptide cyclases, enabling the discovery of other BURP-domain-derived products and development of a bioinformatic method to mine plants for precursor-peptide-encoding genes.
A chemoproteomics profile of the human metabolite 20(S)-hydroxycholesterol exposes its broad connections to the immune system and cancer, revealing it to be a highly selective ligand for the orphan receptor Tmem97 (the σ2 receptor).
The development of a genetic code expansion-based system enables fast protein expression in response to a noncanonical amino acid. The system was implanted into diabetic mice to rescue hyperglycemia with oral delivery of the amino acid.
Discovery of a chemical probe targeting the PWWP domain of NSD2 reveals insight into mechanisms that govern NSD2 localization. The compound and its negative control represent valuable tools for further defining NSD2 biology.
Glyco-PAINT, a super-resolution microscopy approach that images fluorescently tagged glycan interactions with lectins, enables the measurement of sugar–lectin complex densities, residence times and diffusion on cell surfaces.
Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.
During the biosynthesis of triacsin, the two N–N bond formation reactions necessary to create the unique N-hydroxytriazene moiety are catalyzed by a glycine-utilizing hydrazine-forming enzyme and a nitrite-utilizing N-nitrosating enzyme.
Post-translational site-selective formation of boronoalanine in proteins enables applications of boron for binding partner capture, footprinting of interactions with reactive oxygen species, proteolytic control and mapping of transient structures.
Structural analysis of the Pepper aptamer in complex with its cognate HBC or HBC-like color variants reveals that it binds fluorophore molecules via one non-G-quadruplex base quadruple and one noncanonical G·U base pair.
Determination of the cryo-EM structures of active neurokinin-1 receptor bound to substance P or the Gq biased peptide SP6–11 reveals that interactions with the receptor extracellular loops regulate G protein signaling selectivity.
CRISPR–Cas9 genome editing is limited in organisms with inefficient homology-directed repair (HDR), but development of a specialized CRISPR platform conferred increased HDR rates in four noncanonical yeasts to enhance strain engineering.
An approach relying on guide RNA pairs encoding the same edits in both sense and antisense DNA strands is developed to improve the editing capability of prime editing in human cells.
Surface protein tagging and mass spectrometry-based proteomics applied in a rabbit cholera model system identifies proteins involved in Vibrio cholera-host cell interactions and defines a cholera toxin-dependent role for host surfactant protein D.
Trivalent PROTACs are reported as a strategy to increase protein degradation efficacy and therapeutic window by combining avidity of target engagement with cooperativity to form highly favorable and productive ternary complexes.
CoraFluors, a class of macrocyclic terbium complexes for use in time-resolved FRET, exhibit physicochemical properties desirable for biological studies, including characterization of Keap1 ligands and HDAC1 target engagement profiling in live cells.
The development of split-engineered base editors (seBEs) enables small-molecule control over DNA deaminase activity, decreasing off-target effects and offering a generalizable solution for temporal control over precise genome editing.