Longevity protein: a boon for diseases

1 month ago Shruti Goel 0

A gene named after a Greek goddess Klotho, who swung the thread of life plays an important role in the regulation of longevity and metabolism. The Klotho gene is identified as an evident age-suppressing gene in mice. It is known for extending lifespan when overexpressed. It instigates complex composition resembling human premature aging syndromes when suspended. Various investigations on Klotho gene have led to the identification of multiple endocrine axes that regulate the various metabolic processes. Also, an unexpected link between mineral metabolism and aging has been identified.
The Klotho family is located on the surface of cells of specific tissues. It comprises of two receptor proteins. Klotho proteins bind to a family of hormones, known as endocrine Fibroblast Growth Factor (FGF). They are known for regulating critical metabolic processes in the liver, kidneys, and brain, among other organs.

Beta-Klotho

Scientists have divulged the 3D structure of a protein linking to longer lives. It is a type of the Klotho protein and is known as beta-Klotho. It is paving the way for new therapies to treat a wide range of medical conditions. These include diabetes, obesity as well as certain cancers. Researchers from Yale University in the United States revealed this structure, illuminating its serpentine mechanism and curative potential. The researchers used X-ray crystallography technique, providing high-resolution, and 3D sights of this protein.

Klotho-beta binding with galactoside

X-ray Crystallography

The basic aim of X-ray crystallography is to obtain a 3D molecular structure from a crystal. In this, a beam of X-rays undergoes diffraction in many directions, when incident upon the crystalline atoms. A crystallographer measures the angles and intensities of these diffracted beams, producing a 3D picture. This picture depicts the density of electrons within the crystal. X-ray crystallography is the most used technique for developing many scientific fields. The structure and function of many biological molecules such as vitamins, drugs, proteins, and DNA have also been revealed by this technique.
To understand the working of beta-Klotho, this technique was considered much efficient by the research team. Firstly, they deduced that beta-Klotho is the primary receptor binding to FGF21. FGF21 is an essential hormone produced during starvation. When bound to beta-Klotho, it causes weight loss by stimulating the insulin sensitivity and glucose metabolism.

Technique of X-ray crystallography

Helping Diabetes Therapies

The link between beta-Klotho and FGF21 results in guiding the development of therapies for conditions such as type 2 diabetes. Stating the similarities, just like Insulin FGF21 stimulates the metabolism including glucose ingestion. Also, the team proved the point by presenting evidence of how glycosidase evolved into a receptor for a hormone that lowers blood sugar.
Glycosidase is a structurally-related enzyme which breaks down sugar. It is commonly used in roles including degradation of cellulose, hemicellulose, and starch, in antibacterial defense strategies and many other mechanisms. Found in all domains of life, such as in prokaryotes, within the endoplasmic reticulum and Golgi apparatus, etc, it is involved in biosynthesis and degradation of glycogen in the body.

structure of insulin

Hope for multiple diseases

Researchers hold a platform for exploring effective therapies for multiple ailments due to untangling the structure of beta-klotho. Diabetes and obesity can directly be targeted by developing drugs that enhance the pathway. Conversely, there is hope for exploring therapies for conditions such as liver cancer and bone diseases by using agents that block the pathway. One of the researchers said that “The next step will be to make better hormones, make new potent blockers, do animal studies and move forward”.
Further studies on this longevity protein would definitely help to increase the metabolism and work as an anti-aging or age suppressing protein. It would successfully be brought into use and will surely prove to be helpful.

 
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