3D Model of Bax Protein Newly Proposed!

The protein Bax is one of great interest to scientist. Bax is one of the proteins responsible for cell death by puncturing holes in the mitochondria of cells. This in turn causes proteins in the organelle to leak into the cytoplasm of the cell, resulting in cell death through apoptosis. Which some may believe this protein to be troublesome, cell death is sometimes needed. Especially in the situation of cancer patients. Cancer is the over multiplication of cells, if there was a way to use this Bax protein against cancer cells, it would greatly revolutionize cancer treatments. The only problem was that until very recently, scientists did not know what Bax exactly looked like. They knew the crystal structure of the truncated core of the domain, but not the full length structure on the protein.

However, scientists at the Freie Universität Berlin, the University of Tubingen, and the Swiss Federal Institute of Technology in Zurich have developed a 3D model of the Bax protein. With this model, scientists now know how the protein looks and acts. The most significant discovery was that the hairpin at helices 5-6 of the protein form into a clamp-like dimeric structure. This structure is thought to be the mechanism that punctures the mitochondria. The punctures are actually formed by the structure pinching the membrane bilayer. One scientist, Enrica Bordignon, explains how important this discovery is by saying, “If we understand how the Bax protein deforms the membrane and forms pores, we are one step closer to understanding how cells die, and thus one step closer to the development of new cancer drugs which should promote cell death.” If the Bax protein could be better understood and could be used to control the apoptosis of cancer cells, it would be an incredible advancement in the field of cancer treatment research.

Article: http://www.sciencedaily.com/releases/2014/11/141121033230.htm

Significant Research Breakthrough for Lupus, Cancers and Neurodegenerative Diseases

Research teams from the Walter and Eliza Hall Institute combined to discover both the three-dimensional structure of a key cell death protein, Bak, as well as an understanding of the first steps in how Bak causes cell death. Apoptosis, programmed cell death, occurs when chemical signals activate Bak and Bax. The activation of Bak and Bax tells the cell to die by targeting the mitochondria. When apoptosis is working effectively unwanted cells are killed and removed from the body. However, when trouble with apoptosis occurs harmful cells, such as cancer cells, continue to grow or healthy cells die unnecessarily, such as what happens in Alzheimer's disease.

Specifically, the team’s research showed how Bak changes from one form to another form in order to initiate apoptosis. Additionally, the research team discovered how the Bak and Bax protein dimers attach to the mitochondria and perforate the mitochondria. It has been understood that the Bak and Bax dimers open the mitochondrial surface; however, the mechanism for how the dimers perforate the mitochondria was previously poorly understood.

Scientists originally believed that Bak and Bax poked a hole through the surface of the mitochondria; however, the team’s research disproved this belief. Instead the team discovered that the dimers attach onto the oily surface of the mitochondria and crowd the surface until holes form in the surface. What still remains unknown is exactly how the proteins come together to destroy the mitochondria and initiate apoptosis.

I found this article very interesting because this small development will lead to a much greater understanding of apoptosis in the future. Now that researchers are able to understand the structures of the proteins involved apoptosis they have the necessary information to begin advancing towards a deeper understanding of apoptosis, specifically the initiation of the process. This research will be crucial to understanding how to regulate apoptosis to combat diseases such as lupus, cancers and neurodegenerative diseases.  

Main Article: http://www.sciencedaily.com/releases/2014/10/141031121307.htm

Secondary Article: http://www.cell.com/molecular-cell/abstract/S1097-2765(14)00609-1

Secondary Article: http://www.pnas.org/content/111/39/E4076.full