Chinese scientists first in the world to map protein complex

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, or 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 percent of people aged over 50 suffer from the condition, and nearly half of the population over 50 years of age has low bone mass.

“Because of osteoporosis, my mother doesn’t live a good life as she grows old,” said Wang Ming-Wei, a researcher from the Shanghai Institute of Materia Medica under the Chinese Academy of Sciences.

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.

“Like a baby, it keeps moving and thus it’s hard to get to know its structure,” said Zhang Yan, from the School of Basic Medical Sciences of Zhejiang University. “We freeze thousands of protein complexes to 180 degrees Celsius below zero to obtain images.”

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 added.

The image is of extremely high definition, up to 3.0Å, 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.”

The research was published on Friday in the journal “Science.” Wang, Zhang and other scientists in China and from the US together contributed to the work.

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

Comparing the protein complex to an elephant, he said previously people didn’t 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, which can help them to precisely target the site in question.