Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have elucidated the three-dimensional atomic structure of somatostatin, a hormone-regulating substance that inhibits hormone secretion through its receptor somatostatin receptor 2 complex (SSTR2).

Somatostatin is a hormone that inhibits the secretion of growth hormones. It is a hormone related to the intestines and brain and acts on hormone secretion regulation, cell proliferation, and neurotransmission in the brain.

SSTR2 is a membrane protein present in the cell membrane and plays a role in recognizing extracellular somatostatin as a signal and delivering it into the cell.

Despite the importance of somatostatin in-vivo function and disease, the detailed mechanism of how somatostatin binds to receptors on the cell membrane and the three-dimensional atomic structure, which plays an essential role in drug development, was unknown until now.

The team, led by Professor Song Ji-hoon of the Department of Life Sciences, identified the structure of the SSTR2 complex, which binds to somatostatin and inhibits the secretion of various hormones, using a cryogenic electron microscopy technique at 3D atomic resolution. Professor Lee Won-tae at Yonsei University and a research team from PCG-Biotech, a local biotech firm, participated in the study.

Using the study results, the team investigated how somatostatin inhibits hormone secretion through SSTR2.

The team also found out the mechanism of somatostatin binding in each of the isomeric forms by predicting the structures of SSTR1, SSTR3, SSTR4, and SSTR5, isomeric forms of somatostatin receptors (compounds with the same molecular formula but different molecular structures), and using AlphaFold, a structural prediction program using artificial intelligence.

The team said it expects such study results to help develop a method to control acromegaly and brain and spinal cord tumors caused by abnormal hormone secretion.

The study results were published in the journal eLife, on April 22.