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A knot-like RNA from Zika virus is shown to evade digestion by host RNases through its extreme resistance to mechanical unfolding. Weakening the knot mechanically or reducing the likelihood of knot formation lowers the RNase resistance.
A linkage-specific tool for K29-linked polyubiquitin was developed, enabling the discovery that K29-linked ubiquitination participates in multiple cellular pathways, including the proteotoxic stress response and cell cycle regulation.
Design of a bivalent inhibitor containing an ATP-competitive moiety and rapamycin-modified FRB binding ligand that selectively inhibits mTORC1 results in potent and durable inhibition of 4EBP1 phosphorylation and cell proliferation in vitro and in vivo.
Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of SARS-CoV-2.
Degradation-tuning RNAs (dtRNAs) have the capacity to increase and decrease RNA stability in vivo and in vitro. Appending these modules to transcripts allows fine tuning of circuit dynamics, CRISPR interference and paper-based viral diagnostics.
Fragment screening and medicinal chemistry optimization led to development of a small-molecule inhibitor of RING1B–BMI1 E3 ligase, blocking the H2A ubiquitination activity of the Polycomb repressive complex 1 and inducing differentiation in leukemia cells.
Structural biology, computational biology and biochemical analysis revealed the molecular mechanism of transcriptional processing of unnatural base pairs selectively recognized by cellular RNA polymerase.
A genome-mining approach targeted to enzyme domains that co-occur in a single protein (CO-ED) facilitates the discovery and characterization of an oxazolone synthetase involved in the biosynthesis of a series of oxazolone-containing natural products.
Reconstitution studies reveal design principles by which a minimal 3-protein module differentially regulates the dynamics of spatially proximal crosslinked and noncrosslinked microtubules, mimicking microtubule array dynamics in the mitotic spindle.
Two degraders targeting zinc finger transcription factor IKZF2 (Helios) were developed by reprogramming CRL4CRBN E3 ligase, and the pharmacologic degradation of Helios results in Treg destabilization.
A chemically induced dimerization strategy was used to recruit SUMOylation enzymes into condensates, enabling quantification of the effect of phase separation on the activity of a SUMOylation enzyme cascade reaction.
The development of Sulfopin, a highly selective and potent, covalent Pin1 inhibitor that phenocopies Pin1 knockout and regresses tumors in murine and zebrafish models of neuroblastoma as well as in a pancreatic cancer mouse model.
A set of LOV2 circular permutants (cpLOV2) have been engineered to expand the existing optogenetic toolbox. cpLOV2 enables the design of both ON- and OFF-switches to control cell signaling, gene expression, cell fate and cancer immunotherapy.
Liquid glycan arrays (LiGAs), presented on M13 bacteriophage surface proteins through bioorthogonal chemistry, link surface glycans to genetic barcodes in phage DNA, enabling lectin–glycan interaction profiling by DNA sequencing.
The structure of the heme lyase CcmF, an integral membrane protein, reveals a cavity opening toward the extracellular side to receive heme groups from the chaperone CcmE and a surface groove for guiding the substrate protein during heme attachment.
A chemically inducible technique for trapping cytosolic proteins in microtubules (MTs) in cells reveals that soluble proteins can enter the MT lumen by diffusion, while proteins forming a complex with tubulins can be incorporated at MT plus ends.
ABD957 is a potent and selective inhibitor of the ABHD17 family of depalmitoylases that disrupts N-Ras signaling in human acute myeloid leukemia cells and can synergize with MEK inhibition.
Engineering of a blue light-inducible AraC dimerization system in E. coli permits light-dependent, rather than arabinose-based, regulation of gene expression from standard PBAD promoters, enabling temporal and spatial control of bacterial systems.
A substrate-biased activity-based probe technology was developed to enable relatively facile identification of proteases responsible for specific proteolytic events in complex biological milieu, revealing that urokinase regulates CDCP1 proteolysis.