Scientists from the University of Linköping in Sweden and the Cancer Center of Princess Margaret in Toronto for the first time saw the MYC protein, which plays a major role in the development of cancer, is associated with the key protein and controls important functions in cells. The results of their study were published in the journal «Nature Structural and Molecular Biology». New discovery in the long run can help in the development of new drugs that can disrupt MYC function in tumor cells.
MYC protein regulates many important functions in healthy cells, but it often shows excessive activity in aggressive types of tumors, where its function can be compared to the accelerator pedal functions, which stuck. The mechanisms by which the MYC function in a cell, are largely unknown. Therefore, the scientists who conducted the study, wanted to find out how MYC transcription factor interacts with another protein, TATA-binding protein (abbreviated «TBP»). TBP functions as a start button for the expression of many genes in the cell.
MYC was elusive for structural biologists. It is known as "random" protein that moves dynamically between different structures. MYC can bind more than 300 different proteins in a cell. The key to that MYC can communicate so quickly with many other proteins, it is its adaptability and the ability to quickly change the structure.
About 70% of the proteins involved in cancer development, are disordered proteins. If scientists can disrupt the function of these proteins in tumor cells, they may be new ways to treat cancer. However, you first need to understand how they function. One of the challenges facing researchers is that they have to find a state in which the protein. About 70% of the proteins involved in cancer development, are disordered protein is quite stable. It is necessary for the study of its structure at the atomic level. In the current study, they were able to capture an instantaneous image of MYC, associated with the saddle protein TBP, and explore complex protein using crystallography and nuclear magnetic resonance.
Scientists have discovered how MYC binds the parties "saddle» TBP ».
Then they decided to find out whether the found they played in the structure of the biological function of the protein. Scientists have created a MYC mutations, which have been removed various features of binding sites, and examined how this affected the function of the protein, the growth and survival of cells.
They demonstrated that the observed binding sites affect the MYC activity, as well as the growth and proliferation of cells. Disruption of interaction between MYC and TBP sharply reduces the ability of surviving cells.
Scientists have not yet managed to directly portray the dynamic binding site, which has the highest biological function at atomic resolution. For this reason, they combined data from the different methods and had a complex calculation to simulate the interaction between the two proteins. They were used to determine the structure of the AI, which best agrees with the observed data and thus identified a previously unknown binding site. Researchers believe that the MYC helps to increase gene expression, simplifying deployment TBP in the right place at the DNA.