Volume 18 Issue 3, March 2022

The design of biological materials with tunable properties is an emerging challenge for the twenty-first century. A new approach to direct engineered cells to stick together improves biomaterial performance and simplifies self-healing.

Just how chaperones clear protein aggregates is a notoriously impenetrable problem. A new study now shows how single-molecule movies of Hsp104 and Hsp70 chaperones acting on amyloid fibers are the key to revealing their underlying cooperation in time and space.

Cryo-EM structures of Mas-related G-protein-coupled receptors (MRGPRs) that are involved in the allergic reaction and itch response reveal structural insights into their activation mechanism, and offer the potential to discover new therapeutic agents for pain and hypersensitivity reactions.

Synthetic receptor signaling systems have evolved as platforms for user-controlled programming of cellular functions. This Perspective reviews these advances and defines a metrics-based engineering workflow to support future engineering efforts.

Cryo-EM and molecular dynamics simulation analysis of peptide variants of GLP-1 and exendin-4 reveal distinct receptor conformers with unique modes of peptide–receptor engagement.

Cryo-EM structures of the CCR1–G_i complex with N-terminal truncations of the endogenous chemokine CCL15 revealed that the conformational change of Tyr291 in CCR1 regulates β-arrestin signaling.

A computational pipeline linking molecular dynamics simulations and an elastic network model-based method identifies druggable sites in the parathyroid hormone class B GPCR and a nonpeptidic allosteric modulator of receptor signaling in cells.

Cryo-EM structures of sphingosine-1-phosphate receptor with G_i bound and in complex with ligands revealed the key conformations and interactions that mediate β-arrestin bias.

Bacterial populations, programmed to self-assemble by adhesion of nanobody–antigen pairs, can be processed into living materials (LAMBA) that are scalable, self-healing and programmable through functionalization with diverse proteins.

IsoAnalyst is a mass spectrometry-based parallel stable isotope labeling platform that associates labeling patterns with bioinformatic structure prediction in order to connect natural products to their corresponding biosynthetic gene clusters.

Elucidation of the bacterial ceramide biosynthetic pathway reveals that it likely evolved independently from the eukaryotic pathway, as bacteria lack homologs for many of the eukaryotic enzymes and the reactions occur in a different order.

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.

Real-time fluorescence imaging analysis with a reconstitution system revealed binding dynamics of Hsp104/Ssa1/Sis1 chaperones to Sup35 amyloid and two distinct modes of amyloid disaggregation, fragmentation and dissolution.

Fluorescence-quenched substrates, which accurately report on glycoside hydrolase activity, provide real-time activity measurements on α-GALA and α-NAGAL, including in fibroblasts from patients with linked lysosomal storage diseases.

Second-generation engineered soluble ACE2 proteins display enhanced binding to the spike protein of SARS-CoV-2 and operate as ‘decoys’ that interfere with viral infection, reduce lung injury and lower mortality in mouse models.