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.
How phosphorylated ubiquitin activates Parkin
First RNAi meiosis screen in mammals reveals genes essential to generate eggs
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.
Revealing how GPCRs activate Gα proteins.
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.
Structure of the human 20S proteasome with a ligand revealed by cryo-EM
Spliceosome U4/U6.U5 tri-snRNP structure revealed by cryo-EM
Genes in eukaryotic organisms are frequently interrupted by non-coding segments called introns. Before the protein can be produced, the entire length of each gene including the introns, is transcribed to produce precursor messenger RNA (pre-mRNA). An immense and dynamic molecular machine known as the spliceosome then removes the introns and splices the coding segments together to form mature mRNA, which can then be translated into proteins.
Atomic structure of the anaphase-promoting complex (APC/C)
The anaphase-promoting complex (APC/C) is an unusually large multi-subunit complex that has a key role in cell division, controlling chromosome segregation and the cell cycle. Using electron cryo-microscopy (cryo-EM), David Barford and his group in the LMB’s Structural Studies Division have solved the first atomic structure of the APC/C, revealing its molecular architecture in unprecedented detail.
When cells divide they go through a series of phases known as the cell cycle.