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Mapping of protein complex to help patients with osteoporosis
Help target the site precisely in the development of oral medicine for osteoporosis

Chinese scientists have become the first in the world to obtain the near-atomic map of a protein complex, which will aid in the development of oral medicine against osteoporosis.

Parathyroid hormone (PTH) is a classic endocrine hormone released by parathyroid glands to regulate calcium levels in the blood. When the blood lacks calcium, PTH helps it absorb more calcium from the bones. But if PTH becomes too “warm-hearted,” it can cause osteoporosis.

Across the world, 200 million people suffer from osteoporosis. In China, nearly 20 per cent of people aged over 50 suffer from the condition, and nearly half of the population over 50 years of age has low bone mass.

How does PTH become a regulator? A previous study shows PTH binds with a protein called PTH1R, expressed in bone and kidney cells, and the protein complex works to regulate calcium metabolism. However, it had been a mystery what the complex looks like.

The complex is constantly moving, so it is difficult to understand the structure. The researchers froze thousands of protein complexes to negative 180 degrees Celsius to obtain images for analysis.

Besides knowing its structure, scientists also understand how it moves. "Protein complexes are frozen in different postures as they are moving, and by studying these different postures we know how they move," Zhang Yan, from the School of Basic Medical Sciences of Zhejiang University, said.

The image is of extremely high definition, up to 3.0A, equal to 1/30 billion meters. It shows that PTH1R starts to transform after it binds with PTH, and then it delivers messages to “build up bones” or “take calcium out of bones.”

One researcher said comparing the protein complex to an elephant, people did not know the right part to target and they could just do it randomly. But now they know where the elephant’s eyes, teeth and feet are at, it can help them precisely target the site in question.

The research was published in Science.

The results can help to develop oral medicines, hopefully as effective as injections, against osteoporosis.

Source: Shanghai Daily

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