What is Somatostatin?
Somatostatin (SST) is a peptide hormone that is well known for its regulatory effects on endocrine systems. Somatostatin is produced in many locations throughout the body, including GI (gastrointestinal) tract, pancreas, and central nervous system. There are two types of somatostatin that vary in their amino acid lengths. The shorter SST has 14 amino acid chains and mainly works in the brian, and the longer SST has 28 amino acid chains and mainly operates in the GI tract. Not only does SST produce inhibitory impacts on endocrine function, it also can regulate GI tract, exocrine, pancreatic, and pituitary functions. It may also modify neurotransmitters in CNS and distort memories. SST is often used in a NET (neuro emotional techniques)therapy, but excessive use of somatostatin or overproduction of it can cause somatostatinoma, negatively impacting the growth throughout the body and causing hormone disorders, cancers, and neurological diseases.
What is Cryogenic Electron Microscopy?
Cryogenic electron microscopy, also known as cryo-EM, was employed by the researchers to find out the mechanism behind somatostatin and its receptors. Cryo-EM is a high-resolution imaging technique that uses an electron microscope to develop 3D images of small biological structures. In order to perform cryo-EM, researchers freeze an untreated biological sample in a water buffer solution and use an electron microscope with a cold stage. Researchers will apply the specimen “to an EM grid coated with a thin film of an electron-transparent carbon containing small holes” (Pardes). The specimen will then create a thin water layer over the holes in the carbon film, and the layer will contain the biological structures to be imaged. After the grid is blotted, “the grid is quickly plunged into a cold slurry of liquid ethane that is cooled by liquid nitrogen” (Pardes). The specimen contained in water would have frozen so quickly that the ice becomes glasslike (non-crystalline form of ice) and allows researchers to observe the specimen with an electron microscope at an extremely low temperature. Under the electron microscope, the specimen will be hit by the electron beam and this will leave a trace on the image. The computer system will use thousands of similar traces and generate high-resolution 2D images and calculate how different 2D images align with each other, creating high-resolution 3D images.
Image source: https://ccemmp.org/research/what-is-cryo-em/
Cryo-EM used to determine the structure of SSTR2
Recently, professor Ji-Joon Song and his team of researchers from the Department of Biological Sciences determined the cryo-EM structure of SSTR2, one of the receptors of somatostatin, that is bound to the SST-14 peptide (the shorter version). The aim of this study was to determine the specific recognition of the ligand (SST-14) by the receptor molecules and how it transfers signal to the inside of the cell. In order to achieve this, researchers determined the atomic resolution structure of SSTR2 bound with somatostatin 14 peptide in the complex of other signaling proteins (Gαi1/Gβ1γ2 with Gαi1 recognizing scFv16 peptide). The resolution images of the SSTR2 - SST-14 complex are shown below.
Implications
SSTR2, along with many other SST receptors, is associated with many human diseases including growth disorders and cancers. Therefore, the research results will be used to develop biological complexes that can use the mechanism of SSTR - SST complexes to control hypertrophy, treat intracerebral tumors, and treat any brain-associated diseases such as Alzheimer’s. Professor Ji-Joon Song commented: “[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.”
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