Mechanistic basis for protein conjugation in a diverged bacterial ubiquitination pathway.

Ubiquitination is a fundamental and highly conserved protein post-translational modification pathway, in which ubiquitin or a ubiquitin-like protein (Ubl) is typically conjugated to a lysine side chain of a target protein. Ubiquitination is a multistep process initiated by adenylation of the Ubl C-terminus, followed by sequential formation of 2-3 Ubl~cysteine thioester intermediates with E1, E2, and E3 proteins before formation of the final Ubl-lysine isopeptide bond. Ubiquitination is conserved across eukaryotes, and recent work has also revealed at least two related bacterial pathways that perform protein conjugation in the context of antiphage immunity.

A eukaryotic-like ubiquitination system in bacterial antiviral defence.

Ubiquitination pathways have crucial roles in protein homeostasis, signalling and innate immunity. In these pathways, an enzymatic cascade of E1, E2 and E3 proteins conjugates ubiquitin or a ubiquitin-like protein (Ubl) to target-protein lysine residues. Bacteria encode ancient relatives of E1 and Ubl proteins involved in sulfur metabolism, but these proteins do not mediate Ubl-target conjugation, leaving open the question of whether bacteria can perform ubiquitination-like protein conjugation.

Bacterial antiviral defense pathways encode eukaryotic-like ubiquitination systems.

Ubiquitination and related pathways play crucial roles in protein homeostasis, signaling, and innate immunity. In these pathways, an enzymatic cascade of E1, E2, and E3 proteins conjugates ubiquitin or a ubiquitin-like protein (Ubl) to target-protein lysine residues. Bacteria encode ancient relatives of E1 and Ubl proteins involved in sulfur metabolism but these proteins do not mediate Ubl-target conjugation, leaving open the question of whether bacteria can perform ubiquitination-like protein conjugation.

Circadian misalignment in obesity: The role for time-restricted feeding.

Background And Aims: The epidemic of obesity is associated with a substantial, complex and escalating burden of disease. Dietary and lifestyle interventions provide the mainstay of management; however, obesity is multifactorial and challenging to address clinically. Disrupted circadian behaviours, including late eating, are associated with obesity.

Nutritional entrainment of circadian rhythms under alignment and misalignment: A mechanistic review.

Background And Aims: The rising prevalence of obesity is a major international concern and is associated with a substantial burden of disease. Disrupted circadian behaviours, including late and extended eating patterns, are identified as risk factors for obesity. The circadian rhythm synchronises metabolic functions between and within tissues, optimising physiology to integrate with environmental and behavioural cycles.