The Mystery of Titin
ITEB RAS scientists have discovered a mysterious aggregation of the giant protein titin
Scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (ITEB RAS) in Pushchina near Moscow found out that a giant muscle protein – titin – forms aggregates similar to beta-amyloid. The purpose of these units is not yet known. It is possible that they perform some useful functions.
Two recent publications of Pushchinsky biologists in the Journal of Biomolecular Structure and Dynamics and Biophysical reviews are devoted to these assumptions, as well as an explanation of the subtleties of the analytical study of titin.
Titin (titin) is the largest known protein of a living organism. Its molecular weight reaches up to four million daltons, the molecule contains 38 thousand amino acids. It is contained in the muscles, providing their elasticity, strengthening contraction. The existence of titin was not suspected for a long time, because no one could imagine a protein several micrometers in size. It was discovered only in the 1970s by electrophoresis. Since then, titin has been actively engaged in the world. One of the leading scientific groups for its study works at the ITEB RAS in Pushchina.
The layout of the titin in the muscle and its dimensions
(from an article in the Journal of Biomolecular Structure and Dynamics).
– Titin destroys many stereotypes that have developed in science. Many facts about this protein cause surprise even among biologists, – Ivan Vikhlyantsev, head of the laboratory of structure and functions of muscle proteins, Doctor of Biological Sciences, explained to the press service of ITEB RAS.
Titin has not yet been obtained entirely in the form of a separate molecule. It is usually divided into domains or fragments. In the laboratory of Ivan Vikhlyantsev, they learned how to work with large fragments of titin and an entire molecule. It turned out that titin is easily proteolized and also destroyed when heated. This makes it very difficult to work with him. To help other scientists comprehend the subtleties of working with a giant protein, his visualization Ivan Vikhlyantsev, in collaboration with Professor, Doctor of Biological Sciences Zoya Podlubnaya, published a review, thus summing up more than a decade of work. Podlubnaya and Vikhlyantsev discovered in 2004 the largest isoforms of titin in mammalian muscles. Later, they, together with colleagues from the Institute of Biomedical Problems (laboratory of Prof., Doctor of Biological Sciences B.S. Shankman) studied titin changes during space flights. It turned out that the number of long fragments of titin in the muscles decreased in astronauts after long flights, which indicated the development of the disease. And, for example, the gophers after hibernation had even more long fragments, that is, their muscles were healthy.
Now Vikhlyantsev's group is closely engaged in titin aggregates, that is, the folded state of the protein.
– We have shown that titin aggregates are similar to amyloid aggregates that accompany Alzheimer's disease. It was believed that protein aggregates were a sign of the disease. But recently, more and more attention has been paid to functional amyloids that are not associated with diseases," commented the first author of the article in the Journal of Biomolecular Structure and Dynamics, Master of Biology, junior researcher Elmira Yakupova.
– When we talk about functional amyloids, they don't believe us. The stereotype that amyloids are bad is difficult to break," adds Ivan Vikhlyantsev.
Titin has not yet been obtained entirely in the form of a separate molecule. It is usually divided into domains or fragments. In the laboratory of Ivan Vikhlyantsev, they learned how to work with large fragments of titin and an entire molecule. It turned out that titin is easily proteolized and also destroyed when heated. This makes it very difficult to work with him. To help other scientists understand the subtleties of working with a giant protein, his visualization Ivan Vikhlyantsev, in collaboration with Professor, Doctor of Biological Sciences Zoya Podlubnaya, published a review, thus summing up more than a decade of work. Podlubnaya and Vikhlyantsev discovered in 2004 the largest isoforms of titin in mammalian muscles. Later, they, together with colleagues from the Institute of Biomedical Problems (the laboratory of Prof., Doctor of Biological Sciences B.S. Shankman) studied titin changes during space flights. It turned out that the number of long fragments of titin in the muscles decreased in astronauts after long flights, which indicated the development of the disease. And, for example, gophers after hibernation had even more long fragments, that is, their muscles were healthy.
Now Vikhlyantsev's group is closely engaged in titin aggregates, that is, the folded state of the protein.
– We have shown that titin aggregates are similar to the amyloid aggregates that accompany Alzheimer's disease. It was believed that protein aggregates were a sign of the disease. But recently, more and more attention has been paid to functional amyloids that are not associated with diseases," commented the first author of the article in the Journal of Biomolecular Structure and Dynamics, Master of Biology, junior researcher Elmira Yakupova.
– When we talk about functional amyloids, they don't believe us. The stereotype that amyloids are bad is difficult to break," adds Ivan Vikhlyantsev.
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12.07.2017