The pest protein
The structure of the protein that triggers inflammatory processes in the body has been discovered
Anna Kerman, XX2 century, based on materials Medical Xpress: Researchers discover structure of protein associated with inflammation, Parkinson's
The authors of an article recently published in Nature Communication (Malley et al., The structure of iPLA2ß reveals dimeric active sites and suggests mechanisms of regulation and localization) report that they were able to determine the structure of a protein that plays a key role in the development of inflammatory reactions. This discovery can be a starting point in the creation of new approaches to the treatment of a variety of diseases, from heart disease to diabetes, cancer and neurodegenerative disorders, including Parkinson's disease.
A three-dimensional model of the iPLA2ß protein molecule.
A group of scientists led by associate professor of Saint Louis University Sergey Korolev is studying proteins at the atomic level. This is necessary to understand the role that specific proteins play in the body. As part of the new study, the long-studied (but still poorly understood) enzyme calcium-independent phospholipase A2ß (iPLA2ß), which cleaves phospholipids in membranes, was analyzed. When the tissues of the body are damaged, iPLA2ß begins to send signals to the immune system that initiate inflammation. The authors of the new work decided to find out exactly how the protein they are interested in is activated when damaged, how it cleaves substrates and how it "turns off", simultaneously stopping the inflammatory response.
"For the first time [the protein] was described more than 20 years ago in Washington University in St. Louis, – says Korolev. – First, scientists found that this protein plays a role in shaping the response of the cardiovascular system to ischemia or damage.
Then it turned out that [iPLA2ß] is also involved in the process of insulin production and, with certain disorders, can lead to the development of type 1 diabetes mellitus. Even later, less than 10 years ago, the protein was described again – but in a completely different context, during genetic sequencing of patients suffering from neurodegenerative diseases. For example, hereditary mutations in the [corresponding] gene have been found in patients with early onset of Parkinson's disease."
So, scientists have found out that the same iPLA2ß protein plays different roles in different tissues and even in different parts of cells. The more difficult it became to figure out how this protein works. Only one thing was clear – iPLA2ß can be dangerous, since it contributes to the development of cardiovascular diseases, diabetes and even participates in the process of metastasis. On the other hand, the development of an IPLA2ß inhibitor drug could be useful for patients with a variety of diagnoses. But without determining the three-dimensional structure of the protein itself, the creation of a drug capable of suppressing the activity of iPLA2ß turned out to be too difficult.
To determine the molecular structure of the protein, the authors of the new study used X-ray crystallography. According to Korolev, achieving this goal has opened the door to receiving a huge number of answers to questions related to iPLA2ß.
In particular, it turned out that the actual structure of the protein differs significantly from the predicted hypotheses. Previously developed theoretical models of the iPLA2ß structure could not explain all its functions, but now many pieces of the puzzle have fallen into place.
Now Korolev and his colleagues are interested in the role that iPLA2ß plays in the brain. While it is absolutely not clear, but a three-dimensional model of a protein molecule in combination with the results of genetic tests should become a powerful research tool that will help to better understand the principles of the "work" of iPLA2ß in the nervous system and, possibly, learn how to eliminate the harm caused by the protein.
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