In their latest research on the DNA replication machinery from Mycobacterium tuberculosis, Ulla Lang in Meindert Lamers’ group in the LMB’s Structural Studies Division and collaborators at the Harvard School of Public Health in Boston, have revealed the existence of a novel exonuclease that proofreads new DNA as it is synthesised. This newly discovered proofreader prevents mutations in the bacterium and could be a successful drug target.
The existence of an endogenous daily clock in humans is well known: it is what drives the 24-hour sleep/wake rhythm to match the daily cycle of night and day. That this biological circadian rhythm occurs in individual cells, and that they continue to ‘tick’ in a petri dish is now well-accepted scientifically, but the mechanism that allows cellular clocks to keep time remains poorly understood.
The deposition of misfolded proteins is a defining feature of many age-dependent human diseases, including the increasingly prevalent neurodegenerative diseases. Why this happens is unclear. Cells normally strive to ensure that proteins are correctly folded by using powerful and sophisticated mechanisms to maintain protein homeostasis under adverse conditions.
Many of our cells can engulf solid particles and liquid droplets to ingest (swallow) them. Phagocytes ingest invading bacteria and dead cells during infections in the same way that our single-celled distant ancestors engulfed food that they needed for growth. A core group of genes is found within these ancient organisms that is also important for controlling phagocytosis and cell growth in humans.
The structures of many proteins have been extensively studied, however it has proved extremely difficult to investigate the structures of the mRNA molecules that carry the genetic information for these proteins.
How did life first originate on this planet? Even the most minimal cell needs three subsystems: to convey information, to create compartments, and to catalyse metabolic reactions.
Dynactin is a protein complex that activates the dynein motor protein, enabling intracellular transport. It is extremely flexible and has proved very difficult to study by conventional crystallography methods. Now for the first time, research carried out by Andrew Carter and his group in the LMB’s Structural Studies Division, has revealed the structure of this large dynactin complex, using electron cryo-microscopy (cryo-EM).
A research team from the LMB’s Cell Biology division, working with colleagues from the Structural Studies division, has revealed how cells are able to find and tag for degradation the partially synthesised proteins generated when ribosomes occasionally stall.
Cells make more than a hundred thousand new proteins every minute. Once in a while, one of the ribosomes making these proteins stalls, leaving an unfinished protein fragment.