Proteases articles from across Nature Portfolio

Detection of intracellular lipolysaccharide (LPS) activates an immune response initiated by the non-canonical inflammasome. ATGL has now been identified as a negative regulator of this pathway that dampens inflammation by removing LPS’ acyl chains, preventing the activation of inflammatory caspases and cytokines.

To prevent promiscuous protein degradation, proteasomes are initially assembled as inactive complexes. Their activation is autocatalytic and coupled to assembly. Here the authors uncover key aspects of the autocatalytic activation mechanism.

Preclinical characterization of the SARS-CoV-2 M^pro inhibitor RAY1216 shows improved in vivo pharmacokinetics compared with nirmatrelvir.

An uncharacterized metallo-β-lactamase identified in a multidrug-resistant Chryseobacterium indologenes has an atypical lipobox and is potentially lipidated. It has a high-affinity for β-lactams including the last-resort antibiotics, carbapenems.

Antimicrobial resistance is a global health threat and the development of alternative strategies to overcome it is of high interest. Here, the authors report proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery, and apply them for targeting a range of mycobacterial strains, including antibiotic-resistant ones.

Adipose triglyceride lipase (ATGL), an enzyme in fatty acid metabolism, was identified as a negative regulator of the noncanonical inflammasome. ATGL binds to lipopolysaccharide and catalyzes the hydrolysis of fatty acid side chains blocking inflammasome activation.

Detection of intracellular lipolysaccharide (LPS) activates an immune response initiated by the non-canonical inflammasome. ATGL has now been identified as a negative regulator of this pathway that dampens inflammation by removing LPS’ acyl chains, preventing the activation of inflammatory caspases and cytokines.

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.

Medicinal drugs can cross-react with gut bacterial proteins, but the identification of these off-target interactions is difficult. Multi-omic approaches enabled the discovery of a bacterial peptidase that is inhibited by diabetic drugs and unexpectedly influences bacterial fitness within complex microbial communities via a non-proteolytic mechanism.

Most engineered bacteria are designed to grow and function in a free-swimming state. A new method enables engineered bacteria to reversibly transition into a biofilm state.