Context:

• Scientists have unveiled the 3D structure of a protein linked to longer lives, paving the way for new therapies to treat a wide range of medical conditions, including diabetes, obesity and certain cancers.

Klotho proteins:

• Klotho proteins play an important role in the regulation of longevity and metabolism.
• Researchers from Yale University in the United States revealed the three-dimensional structure of one of these proteins, beta- Klotho, illuminating its intricate mechanism and therapeutic potential.
• The Klotho family of two receptor proteins are located on the surface of cells of specific tissues.
• The proteins bind to a family of hormones, designated endocrine FGFs, that regulate critical metabolic processes in the liver, kidneys, and brain, among other organs.

X-ray crystallography used:

• To understand how beta-Klotho works, the research team used X-ray crystallography, a technique that provides high- resolution, 3D views of these proteins.
• The researchers’ analysis yielded several insights.
• First, beta-Klotho is the primary receptor that binds to FGF21, a key hormone produced upon starvation.
• When bound to beta-Klotho, FGF21 stimulates insulin sensitivity and glucose metabolism, causing weight loss.

Can help in diabetes therapies:

• This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as type 2 diabetes in obese patients.
• Like insulin, FGF21 stimulates metabolism including glucose uptake.
• FGF21 has 10 times higher potency and cellular activity.

Source:TH