Date Published: 11 February 2011

Cancer Researchers describe the structure of the anaphase-promoting complex (APC/C) molecule

Recent research described in the paper "Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor" just published today in the prestigious scientific journal Nature describes the structure of the anaphase-promoting complex (APC/C) molecule, which is known to play an important role in controlling cell division.

Understanding of the cell division cycle is vital for cancer research. An accurate 3D model of a molecule associated with breast cancer and with colon cancers has been created for the first time as part of the recent work. This three dimensional model will enable scientists to investigate how the molecule interacts with other proteins, how errors in its DNA code can change its structure and how anti-cancer drugs can block or enhance the molecule's behaviour.

APC/C is a very large molecule created by joining together 13 different proteins into a kind of molecular machine involved in regulating the cell cycle – a process which, if it malfunctions, can lead to cancer by allowing cells to multiply out of control. Using a number of different techniques such as electron microscopy, protein crystallography, nuclear magnetic resonance (NMR) spectroscopy and molecular biology, this research has now revealed how most of the 13 different components fit together and how the APC/C complex recognises and then degrades targeted proteins, called cyclins and securins.

Dr Mark Williams, Director of the Institute of Structural Molecular Biology's Biophysics Centre at Birkbeck, carried out the nuclear magnetic resonance spectroscopy – a technique closely related to the MRI scans used in hospitals, but using a magnet ten times as strong.

" In many ways it is like using a supercharged FM radio – NMR detects and characterises molecules by the frequency of radio waves emitted by the nuclei of their atoms," explained Dr Williams.
" They may differ in frequency by as little as 1 part in 10 million but even in a very large molecule like a protein we can identify the particular nucleus that gives rise to each signal. This ability to discriminate different nuclei enables us to detect the changes that arise from molecules binding together and, in favourable cases, to determine 3D structures."

More information:
The Institute of Cancer Research (ICR) is a major European cancer research centre that has been ranked as the UK's top academic research centre based on the results of the Higher Education Funding Council's Research Assessment Exercise. It works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. For further details see www.icr.ac.uk
The paper, Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor, is available to view on Nature.

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