Scientists unveil the three
dimensional structure of one of the Klothos proteins, which are known for their role in regulating
longevity and
metabolism. This study has paved the way to understanding the intricate mechanism behind the β-Klotho
protein
and its therapeutic potential.
Snakes are usually known for their S-shaped movement, but scientists wanted to unlock the mechanism behind a snakes ability to propel themselves forward in order to navigate confined spaces. Researcher, Dr. Bruce Jayne, has already unlocked the mechanism behind three types of snake movements, the concertina, serpentine, and sidewinding. In his recent study published in the Journal of Experimental Biology, Dr. Jayne and Dr. Steve Newman, touch on the straightforward movement of snakes called “rectilinear locomotion.”
The Klotho family is comprised of two receptor proteins that are located on the surface of specific tissue cells. These receptors bind to FGF family endocrine hormones and regulate metabolic processes in the liver, kidneys, brain, and other organs. In this study, recently published in Nature, scientists wanted to understand how the β-Klotho protein works, so they performed X-ray crystallography. This technique produced a three-dimensional view of this protein and discovered that β-Klotho binds to FGF21. FGF21 is a hormone that is produced upon starvation and when it is bound to beta-Klotho, it stimulates insulin sensitivity and glucose metabolism that stimulates weight loss. Researchers also indicated that in previously published animal studies and clinical trials, FGF21 has been shown to increase the burning of calories without changing food intake. This study has elucidated mechanisms on how to improve the biological activity of FGF21. The paper also describes a new variant of FGF21 that is about 10 times higher potency and cellular activity. These new insights could lead to the development of therapies for multiple diseases such as diabetes, some cancers, and obesity.
Structures of β-klotho reveal a 'zip code'-like mechanism for endocrine FGF signaling (January 2018)
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