YouTube video by World Economic Forum

Postdoctoral Researcher Salary £42,694 per annum  MRC Laboratory of Molecular Biology, Cambridge, UK We are recruiting a Postdoctoral Researcher to...

Read the full text of Prime Minister Mark Carney's speech about a shakeup of the global order and role of middle powers at the World Economic Forum in Davos, Switzerland.

Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.

Protein degradation by the proteasome is central to cellular homeostasis and has been studied extensively using biochemical and structural studies. Despite an in-depth understanding of core proteolytic activity, it has remained largely unresolved how individual proteasomes process substrates inside living cells where many substrate types and co-factors exist. Here, we establish a live-cell single-molecule imaging approach that enables direct visualization and quantification of protein degradation by individual proteasomes. Using this approach, we find that substrate identity, folding and protein-protein interaction have a surprisingly modest impact on processing efficiency, whereas the mode of substrate engagement greatly impacts substrate processing; degradation initiated from protein termini typically proceeds rapidly and with high processivity, whereas internal engagement constitutes a distinct processing mode that exhibits poor processivity and a specific requirement for the AAA+ family ATPase p97/VCP. Furthermore, degradation initiated from opposite termini proceeds with asymmetric rates in a sequence-dependent manner, demonstrating that directionality is an important feature of proteasomal processing in vivo. Notably, poly-glutamine substrates associated with neurodegenerative disease are efficiently degraded from one terminus but resist degradation when engaged from the opposite terminus, highlighting the importance of substrate engagement mode. Together, our results show that different modes of substrate engagement lead to different proteasomal processing outcomes in vivo and revise the prevailing view of the proteasome as a uniform degradation machine. ### Competing Interest Statement The authors have declared no competing interest.

Background The capacity of cells to retain a memory of previous signals enables acquisition of unique fates and adaptation to their environment. The underlying gene expression memory can arise from mu...

AI-powered pipeline converts antibodies into functional intrabodies, enabling live-cell imaging of peptides and histone marks.

This video is the culmination of several years attempting to: (1) Figure out best practices for modeling protein-protein interactions; (2) Understand the This video is the culmination of several years...

In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

Men’s race will visit Edinburgh, Carlisle, Keswick, Liverpool, Welshpool and Cardiff, while women will head from Leeds to Manchester, then to Sheffield and also includes a central London stage