Professor Ji-Joon Song and his team of researchers from the Department of Biological Sciences determined the 3D structure of somatostatin and its receptor, somatostatin receptor 2 (SSTR2). In an interview with the KAIST Herald, Professor Song kindly explained his research.
Somatostatin is a hormone that inhibits the secretion of growth hormones and is related to the gut and brain, and acts on hormone secretion control, cell proliferation, and brain neurological substances delivery. Professor Song explained, “Somatostatin is a membrane protein that receives signals from outside, and then converts them into internal signals. [Somatostatin is] located in the cytoplasmic membrane and is composed of seven transmembrane proteins. So, it’s waiting for some signal; in this case it’s the somatostatin peptide 14, […] known for inhibiting the signal for cell growth.”
Professor Song’s research team used cryo-Electron Microscopy (CEM) to identify the mechanism by which somatostatin inhibits hormone secretion through SSTR2. “Cryo-electron microscopy is called ‘cryo’ because you are actually looking at this molecule at the cryogenic condition which is around minus 190˚C,” Professor Song explained. “Basically, you can see the biomolecule, which is complex in this case, [since it is] at the atomic level.”
Explaining his research, he responded that “the question was how receptor molecules recognize this ligand and transfer the signal to the inside of a cell. In order to understand how this somatostatin receptor recognizes this somatostatin ligand, we determined the atomic resolution structure of the somatostatin bound receptor in the complex of another signaling protein called the G-protein using cryo-electron microscopy.”
This research seemed rather tangential to Professor Song’s usual fields of research at first. “Frankly, my research area is largely two different areas. One is epigenetic gene regulation, and the other one is neurodegenerative diseases. Although somatostatin is not directly related to the topics I mentioned, we have been investigating how this protein molecule is functioning inside the cell.” This led to a collaboration with Professor Weontae Lee of Yonsei University. “[He is] an expert in membrane protein,” Professor Song remarked, “and I had technology, which is cryo-electron microscopy. So, we actually teamed up […] to study this.”
The results of this study are expected to be used to develop substances that can use the mechanism of action of somatostatin receptors to control terminal hypertrophy, treat neurocerebral secretion tumors, and improve brain function. “Significance of this research is that the somatostatin receptor 2 is highly implicated in a lot of diseases,” Professor Song commented. “[A] few years ago, Prof Seunghee Lee in our department showed that somatostatin is highly implicated in neurodegenerative disease. The level of somatostatin level is lowered down in the [patients with] Alzheimer’s disease. [The significance of this research] is not only about how somatostatin interacts with its receptor, but also how there’s potential — because it’s structural information — that tells how these ligands specifically recognized by this receptor can be utilized.”