Debilitating illnesses such as autoimmune diseases and cancer are deadly because they are difficult to treat. Besides, finding appropriate therapies and effective drugs has been a struggle within the health care industry as the underlying mechanisms of these illnesses are not fully understood. If we can understand how molecules in the body interact and cause these illnesses, it would help researchers design new drugs that target the molecular mechanisms behind autoimmune diseases and cancer.

A group of scientists from Ritsumeikan University, Yokohama City University, and Osaka University in Japan have recently made significant progress in this direction. Their recent study, published in Nucleic Acids Research, reveals the molecular mechanisms behind the functioning of a specific protein—Ets1—involved in both autoimmune disease as well as cancer. The structure of this protein includes a region, termed the intrinsically disordered region (IDR), that can be modified at several sites; these modifications can completely change the effective function of the protein.

Depending on the modification, the protein either binds or does not bind to DNA, causing genes to turn on or off.

The lead author of the study, Assistant Professor Kota Kasahara of Ritsumeikan University’s College of Life Sciences, says, “Although it is known that the IDRs of proteins are of importance for a variety of biological processes, the physics of IDRs have not been well understood.”

The researchers found that when phosphoryl groups attach to a part of the Ets1 IDR that is rich in the amino acid serine, it is no longer capable of binding to DNA; this in turn affects the expression of certain genes. Their study thus provides a striking example of how an IDR works.

The proposed protocol can be successfully applied to other similar molecular systems. Kasahara explains, “Since modifications such as phosphorylation on the IDR are well-known mechanisms for gene-expression regulation and relevant to many diseases, the molecular mechanisms behind a variety of diseases are expected to be studied through the application of our protocol.”

This study provides useful insights into the biophysical behaviour of IDRs that can have benefit advances in the fields of protein science, molecular biology, medical science, and life science.