Structural insights into the catalysis and regulation of E3 ubiquitin ligases

Covalent attachment (conjugation) of one or more ubiquitin molecules to protein substrates governs numerous eukaryotic cellular processes, including apoptosis, cell division and immune responses. Ubiquitylation was originally associated with protein degradation, but it is now clear that ubiquitylation also mediates processes such as protein–protein interactions and cell signalling depending on the type of ubiquitin conjugation. Ubiquitin ligases (E3s) catalyse the final step of ubiquitin conjugation by transferring ubiquitin from ubiquitin-conjugating enzymes (E2s) to substrates. In humans, more than 600 E3s contribute to determining the fates of thousands of substrates; hence, E3s need to be tightly regulated to ensure accurate substrate ubiquitylation. Recent findings illustrate how E3s function on a structural level and how they coordinate with E2s and substrates to meticulously conjugate ubiquitin. Insights regarding the mechanisms of E3 regulation, including structural aspects of their autoinhibition and activation are also emerging

The Battle for a Sustainable Food Supply

Since the time that Homo sapiens took up farming, a battle has been waged against pests and diseases which can cause significant losses in crop yield and threaten a sustainable food supply. Initially, early control techniques included religious practices or folk magic, hand removal of weeds and insects, and “chemical” techniques such as smokes, easily available minerals, oils and plant extracts known to have pesticidal activity. But it was not until the early twentieth century that real progress was made when a large number of compounds became available for testing as pesticides due to the upsurge in organic chemistry. The period after the 1940s saw the introduction of important families of chemicals, such as the phenoxy acid herbicides, the organochlorine insecticides and the dithiocarbamate fungicides. The introduction of new pesticides led to significant yield increases, but concern arose over their possible negative effects on human health and the environment. In time, resistance started to occur, making these pesticides less effective. This led agrochemical companies putting in place research looking for new modes of action and giving less toxic and more environmentally friendly products. These research programmes gave rise to new pesticide families, such as the sulfonylurea herbicides, the strobilurin fungicides and the neonicotinoid insecticide classes