Volume 20 Issue 4, April 2024

The integrated stress response affects cell survival or death under stress conditions, and depends on the activity of the eukaryotic translation initiation factor eIF2B. New research identifies a protein helix that modulates this response by controlling the structural states of eIF2B.

Traditional production of therapeutic secretory proteins often experiences delays between protein synthesis and therapeutic effects. An inducible protease-dependent protein secretion technique allows the immediate secretion of pre-translated biotherapeutic agents after exposure to chemical cues, tumor-specific antigens or photons.

Macromolecules can undergo liquid–liquid phase separation to form condensates that have critical roles in biological functions and dysfunctions. A new study demonstrates that differences in micropolarity between components is a prime determinant of the multiphasic architecture of biomolecular condensates.

An integrative approach has now enabled elucidation of the complete biosynthetic pathway of a prominent saponin adjuvant. Reconstruction of the whole biosynthetic pathway in a heterologous host provides new perspectives for the biotechnological supply of this immunostimulant.

BURP-domain proteins belong to an emerging class of autocatalytic copper-containing proteins that modify themselves after synthesis. Now, a report explains how their structure and metal coordination sphere control the installation of crosslinks within the core peptide, and shows how nature leverages mechanistic paradigms to create diversity.

Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.

LIS1 is an essential cofactor for the assembly of the cytoplasmic dynein transport machinery. How LIS1 binding affects dynein motility was unclear. Single-molecule experiments reveal that Pac1 (the yeast homolog of LIS1) binding reduces dynein speed by slowing its detachment from microtubules and does not disrupt the mechanism by which it generates force.

Sulfated compounds produced collaboratively by the microbiome and the host have important biological functions. This Review highlights the production of select sulfated carbohydrates, amino acid derivatives and steroidal metabolites and discusses their influence on health. The Review also explore potential roles of sulfated molecules in disease detection, prevention and treatment.

Hydrogen–deuterium exchange–mass spectrometry and cryo-EM analysis revealed an allosteric mechanism involving the conformation of a single α-helix that controls the global conformation and activity of eIF2B, the core molecular machine of the integrated stress response.

A controllable protease-based protein secretion platform was developed for the rapid delivery of user-defined therapeutic protein secretion in response to FDA-approved drugs, tumor antigen and light, enabling cell-based precision therapies.

Ye et al. reveal the critical role of micropolarity in controlling the structure and miscibility of subcompartments in multiphasic biomolecular condensates, thereby providing new insights into multiphasic condensation regulation.

Hernandez-Candia et al. introduce BTBolig, a chemical-based tool to manipulate biomolecular condensates, and CoSMo, a method for control of condensate maturation. When used together, the authors observe dynamic interactions of condensates with protein chaperones.

Structural analysis of a type III effector protein CteC reveals that it represents a unique ‘D-E’ family of PARP-like ADP-ribosyltransferases, which harbors chimeric features from the enzymes of the R-S-E and H-Y-E classes.

Methyl jasmonate in the root volatile organic compounds (rVOCs) signals to the soil microbiome to form biofilms with altered composition that benefits plant growth. This cross-kingdom VOCs-mediated signaling expands the zone of rhizosphere influence.

The cryo-electron microscopy structure of the GPR101–Gs complex reveals the mechanism for its constitutive activity and facilitates the screening and identification of GPR101 ligands with rejuvenating potential.

Vaccine immunoadjuvants are central to vaccine efficiency. Now, the complete characterization of the biosynthetic pathway of QS-21, a potent immunoadjuvant produced by the Chilean soapbark tree, has been reported. These findings open the door to heterologous production of QS-21 and new-to-nature adjuvants.

Zhang et al. determine multiple cryo-electron microscopy structures of inactive monomeric and active tetrameric short prokaryotic Ago/TIR–APAZ (SPARTA) complexes, providing structural basis of SPARTA assembly and activation that will facilitate the development of SPARTA-based biotechnological tools.

Structural analysis of Crenotalea thermophila SPARTA reveals that guide-mediated target binding releases the auto-inhibition of SPARTA imposed by an acidic tail and triggers substantial conformational changes, resulting in the oligomerization of short Ago and TIR for SPARTA activation.

Lis1 binding to the AAA+ ring of dynein increases the microtubule affinity and slows dynein motility. Lis1 binding to the stalk of dynein restricts the sliding of the coiled coils and slows detachment from microtubules under load.

BURP-domain proteins are an unexplored family of plant-specific, copper-dependent peptide cyclases. Here the authors show that a BURP-domain protein has a particular protein fold, investigate its mechanism and provide evidence for intramolecular modification in RiPP biosynthesis.