the endoplasmic reticulum
in green, mitochondria in red,
and chromosomes in blue
Credit: Wellcome Images
Researchers say they’ve uncovered the structure of one of the most important protein complexes involved in cell division, and their finding has implications for cancer treatment.
The team mapped the anaphase-promoting complex (APC/C), which performs a wide range of tasks associated with mitosis.
The researchers believe that seeing APC/C in unprecedented detail could transform our understanding of how cells divide and 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 David Barford, DPhil, of the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK.
“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.”
Dr Barford and his colleagues detailed their discovery in Nature.
The researchers reconstituted human APC/C and used a combination of electron microscopy and imaging software to visualize it at a resolution of less than a billionth of a meter.
The resolution was so fine that it allowed the team to see the secondary structure—the set of basic building blocks that combine to form every protein. Alpha-helix rods and folded beta-sheet constructions were clearly visible within the 20 subunits of the APC/C, defining the overall architecture of the complex.
Previous studies led by the same team had shown a globular structure for APC/C in much lower resolution, but the secondary structure had not been mapped.
Each of the APC/C’s subunits bond and mesh with other units at different points in the cell cycle, allowing it to control a range of mitotic processes, including the initiation of DNA replication, the segregation of chromosomes along spindles, and cytokinesis. Disrupting each of these processes could selectively kill cancer cells or prevent them from dividing.
“The fantastic insights into molecular structure provided by this study are a vivid illustration of the critical role played by fundamental cell biology in cancer research,” said Paul Workman, PhD, of The Institute of Cancer Research, London.
“The new study is a major step forward in our understanding of cell division. 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 outcomes for cancer patients.”
