The atomic structure of the 170 kDa membrane protein gamma-secretase, a membrane protein complex that has an important role in Alzheimer’s disease, has been solved using single-particle electron cryo-microscopy (cryo-EM) by Sjors Scheres’ group in the LMB’s Structural Studies Division. This demonstrates for the first time that high-resolution reconstruction of such small molecules can be achieved using cryo-EM.
New research from the LMB’s Cell Biology and Structural Studies Divisions has answered a long-standing problem in molecular biology: how does the ribosome decode the signals to stop protein synthesis? In cells, all proteins are produced by ribosomes that ‘read’ messenger RNA (mRNA) one codon, or three nucleotides, at a time. Protein translation terminates when a ribosome reaches one of three nucleotide sequences that encode for stop codons.
In a long-standing collaborative effort, groups at MRC Harwell, the LMB, and the University of Oxford have discovered a new genetic mechanism in the circadian body clock that could have important implications for research in mental health and psychiatric disease. Biological clocks run in all our cells, controlling the timing of a number of crucial daily body functions such as core body temperature, hormone production and brain wave activity.
Early-onset Parkinson’s disease arises when the Parkin protein, an E3 ubiquitin ligase, cannot be activated and remains in a permanently ‘off’ state in neurons. Despite the importance of Parkin activation, until recently no-one has understood how the protein could be switched on. David Komander’s group, in the LMB’s Protein and Nucleic Acid Chemistry Division, has now revealed the structure of Parkin bound to an activator, phospho-ubiquitin.
During fertilisation, an egg and a sperm fuse to form a new embryo. To create the egg, a precursor cell called an oocyte undergoes meiosis: a specialised form of cell division in which half the chromosomes are separated away leaving exactly the right number of chromosomes in the egg. Meiosis in human oocytes is highly error-prone, which can cause the egg to have the wrong number of chromosomes.
G protein coupled receptor (GPCR) mediated signalling is one of the largest and the most diverse signalling pathways in cellular systems. Human GPCRs sense various signals and activate different Gα proteins to trigger distinct cellular responses. This signalling pathway is important for a broad range of processes such as regulation of the immune system, neurotransmission, vision, taste, and smell.