Cell division ‘master key’ protein structure revealed

One of the most important proteins found in nature has been mapped by scientists from the Institute of Cancer Research. Images of anaphase-promoting complex (APC/C) – which performs a range of vital tasks associated with mitosis – will help scientists understand exactly how cells copy their chromosomes and divide, and could reveal binding sites for future cancer drugs. “It’s very rewarding to finally tie down the detailed structure of this important protein, which is both one of the most important and most complicated found in all of nature,” said Dr David Barford, Professor of Molecular Biology and leader of the Nature study. “We hope our discovery will open up whole new avenues of research that increase our understanding of the process of mitosis, and ultimately lead to the discovery of new cancer drugs.” Researchers reconstituted human APC/C, using a combination of electron microscopy and imaging software to visualise the gigantic protein at a resolution of less than a billionth of a metre. This fine resolution allowed researchers to see the protein’s secondary structure, a set of basic building blocks which combine to form every protein. Alpha-helix rods and folded beta-sheet constructions were clearly visible with the 20 subunits of the APC/C, defining the overall architecture of the complex. Each subunit bonds with other units at different points in the cell cycle, allowing it to control a range of mitotic processes, including initiating DNA replication, segregation of chromosomes along spindles, and the splitting of one cell into two. Disrupting these processes could selectively kill cancer cells, or prevent them from dividing. “This new study is a major step forward in our understanding of cell division,” said Professor Paul Workman, Interim Chief Executive. “When this process goes awry it is a critical difference that separates cancer cells from their healthy counterparts. Understanding exactly how cancer cells divide inappropriately is crucial to the discovery of innovative cancer treatments to improve outcome for cancer patients.” “Figuring out how the fundamental ‘nuts and bolts’ of cells work is vital if we’re to make progress understanding what goes wrong in cancer cells and how to tackle then more effectively,” said Cancer Research UK Science Information Manager, Dr Kat Arney. “Revealing the intricate details of biological shapes is a hugely important step towards identifying targets for future cancer drugs.” Molecular architecture and mechanism of the anaphase-promoting complex https://www.youtube.com/watch?v=Jxqws38lwjQ