Elusive Cancer-Related Protein Captured In Flight
Arthur T Knackerbracket has found the following story:
Scientists have for the first time seen how the MYC protein, which plays a central role in cancer, binds to a key protein and controls important functions in the cell. The study, published in Nature Structural and Molecular Biology, is a collaboration between scientists at Linkiping University, Sweden, and the Princess Margaret Cancer Center in Toronto, Canada. The new discovery may in the long term help in the development of new cancer drugs that disrupt the function of MYC in tumour cells.
The MYC protein regulates many important functions in healthy cells. But MYC is often extremely overactive in aggressive tumours, where its function can be likened to that of an accelerator pedal that has got stuck. The mechanisms by which MYC functions in the cell are largely unknown. The scientists who carried out the present study, therefore, wanted to find out how the transcription factor MYC interacts with another protein, the TATA-binding protein (abbreviated "TBP"). TBP acts as a starting button for the expression of many genes in the cell.
MYC, however, has proved to be elusive for structural biologists. It is what is known as a "disordered" protein, which constantly shifts between different structures in a very dynamic manner. MYC can bind to over 300 different proteins in the cell. The key to MYC being able to interact with so many other proteins so rapidly is probably its adaptability and its ability to change structure in a flash.
[...] The scientists have not been able to directly image the dynamic binding site that has the greater biological function at atomic resolution yet. For this reason, they combined data from different methods and carried out advanced calculations in a supercomputer to model the interaction between the two proteins. They used AI to home in on the structure that agrees best with the observed data and in this way identified a previously unknown binding site. The researchers believe that MYC helps to increase gene expression by making it easier to place TBP at the correct location on the DNA.
Journal: Yong Wei, Diana Resetca, Zhe Li, Isak Johansson-i...khe, Alexandra Ahlner, Sara Helander, Amelie Wallenhammar, Vivian Morad, Brian Raught, Bjirn Wallner, Tetsuro Kokubo, Yufeng Tong, Linda Z. Penn, Maria Sunnerhagen. Multiple direct interactions of TBP with the MYC oncoprotein[$]. Nature Structural & Molecular Biology, 2019; DOI: 10.1038/s41594-019-0321-z
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