A new spatial biology technique enables isolation and analysis of specific cells from live tissue.

Graspetides are an important class of ribosomal natural products with potent bioactivities. New structural information provides insights into substrate recognition and catalysis, including a rare glimpse into the interactions between a tailoring enzyme and the core of the precursor peptide.

LYTACs induce selective degradation of extracellular proteins by recruiting them to cellular receptors that mediate delivery to the lysosome. Recent development of GalNAc-LYTACs and MoDE-As targeting the liver-specific ASGPR enables cell-type-restricted lysosomal protein degradation and reveals new LYTAC design principles.

Dan Tawfik suddenly left us on 4 May, 2021. His scientific intuition led him to articulate, and solve, many key questions related to protein chemistry and molecular evolution. Although science, particularly for his students, postdoctoral fellows and colleagues, is dimmer after his loss, his legacy will persist.

A Correction to this paper has been published: https://doi.org/10.1038/s41589-021-00867-7.

The structure of a giant ubiquitin E3 ligase sheds light on its activation in a substrate-dependent manner and shows how a single E3 enzyme uses distinct recognition modules to confer substrate specificity.

Liquid–liquid phase separation, yielding membraneless organelles, allows for the sequestration and functional insulation of cellular proteins. A modularly built, synthetic membraneless organelle platform enables efficient control over endogenous cellular activities by knockdown of protein function or controlled protein release.

RNA knot-like structures function as an efficient physical barrier to RNA exoribonucleases. Single-molecule mechanical manipulation is used to unfold these structures and unravel the cause of their unusual mechanical resistance from a different direction.

Different ubiquitin chain types serve as distinct cellular signals. A new synthetic antigen-binding fragment, sAB-K29, specifically recognizes K29-linked diubiquitin and links K29 chains to proteotoxic stress and their accumulation in midbodies during mitosis.

Current antibody discovery technologies are limited in terms of their efficacy, accessibility, and scalability. The AHEAD system addresses these limitations by presenting an accelerated evolution workflow for antibody engineering that combines autonomous gene diversification with protein display technology.

A rationally designed class of mTORC1 inhibitors combines the selectivity of rapamycin with the potency of mTOR kinase inhibitors.

Over the past two decades, inhibitors of the polycomb repressor complex (PRC) have been driven from bench to bedside. New chemical compounds targeting the RING1B in polycomb repressor complex 1 (PRC1) add important tools to regulate polycomb functions.

Heme-containing proteins support a broad range of cellular functions. A new crystal structure explains how an integral-membrane heme lyase attaches the hydrophobic heme to soluble proteins.

Extracellular peptidoglycan-linked polysaccharide modifications mediate cell morphology, division, and autolysis in some Gram-positive bacterial pathogens. A new study shows that the degree and location of a specific modification controls peptidoglycan hydrolysis and placement of the axis of cell division.

The development of chemical tools and small-molecule inhibitors enables the resolution of critical cellular processes with high spatial and temporal precision.

Liquid–liquid phase separation can increase the rate of enzyme activity by concentrating reactants together. A phase-separating SUMOylation cascade offers conceptual and quantitative insight into the mechanisms underlying the activity enhancement.

The use of bacterial biofilms provides a bioplastic that is biodegradable, water processable, and coatable, opening new avenues for plastic alternatives.