Ligases articles from across Nature Portfolio

Asparaginyl ligases have been utilized as valuable tools for protein engineering, such as through site-specific bioconjugation or surface modification, however, their application is limited due to time-consuming preparation processes and unstable activities. Here, the authors develop a truncated protein ligase OaAEP1-C247A-aa55-351 from an OaAEP1-C247A mutant, which simplifies the preparation steps, tolerates a wider pH range, and enhances the catalytic activities by using efficient recognition and nucleophile motifs.

The ubiquitin E3 ligase UBR4 is a key component of the ubiquitin N-degron pathway, but the domain that catalyzes ubiquitin transfer remains unknown. Here the authors identify its unorthodox E3 module and characterize its structure and ubiquitin transfer mechanism.

Here, using structural and biochemical data, the authors provide a comprehensive overview of Okazaki fragment maturation in Escherichia coli, demonstrating a relay of events among the involved enzymes regulating an efficient four-point molecular handover.

Decreased activity of the E1 ubiquitin-activating enzyme UBA1 can contribute to aging and diseases like Alzheimer’s and VEXAS syndrome. Here, the authors found that auranofin, a rheumatoid arthritis drug, can significantly boost UBA1 activity.

The modification of proteins with the small protein ubiquitin constitutes a Daedalian system of posttranslational modifications in every eukaryotic cell, which is often referred to as the ubiquitin code¹. Here we consider the scale and complexity of the ubiquitin system in light of recent developments.

Under steady-state conditions, the E3 ubiquitin ligase Parkin is localized to the cytosol in an autoinhibited state. Two recent studies describe the mechanism of Parkin activation by phosphorylation via structural rearrangement of the Ubl and RING2 domains, explaining how the RING2 domain is released from the core of Parkin to allow for ubiquitination of its substrates.

The cellular response to amino acids is controlled at the molecular level by TORC1. While many of the elements that participate in TORC1 signaling are known, we still have no clear idea how cells sense amino acids. Two recent studies found that leucyl-tRNA synthetase (LRS) is a leucine sensor for TORC1, in both yeast and mammalian cells.