Avi Blizovsky
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Retroviruses are among the most insidious and cruel agents of disease, responsible, among others, for AIDS and certain types of viral hepatitis and leukemia. The name retrovirus is given to a virus that carries its genetic load in RNA molecules and not in DNA like most other viruses and all animals, humans and plants on Earth. Since viruses cannot reproduce on their own, they penetrate living cells, combine the viral genetic material with that of the cell, and thus, in effect, take over the cell and enslave it to their needs, so that the cell produces more and more viruses in their image and likeness. This process causes the disease of the organism whose cells have been taken over by the viruses.
To take over the cell, the viruses must penetrate it. Retroviruses do this using special protein clumps displayed on the virus envelope. These proteins cause the virus envelope to fuse with the cell membrane, which allows the viral genetic material to penetrate into the cell and integrate into its genetic cargo. Preventing this fusion may prevent retroviruses from entering cells, which means preventing the diseases they cause. An important step in this direction was made recently, when a team of scientists from the Weizmann Institute of Science, led by Dr. Deborah Fass from the Department of Structural Biology, working in collaboration with scientists from the Max Planck Institute for Biochemistry in Germany, succeeded in deciphering the three-dimensional spatial structure of the viral proteins that enable the the fusion These findings were recently published in the scientific journal "Records of the American Academy of Sciences" PNAS.
Many scientists, from different parts of the world, have tried for a long time to decipher the three-dimensional spatial structure of the viral proteins involved in the penetration of retroviruses into cells. The accepted way to decipher the XNUMXD spatial structure of a protein is based on the creation of crystals from the studied protein. These crystals are irradiated with X-rays ("x-rays"). The radiation returning from the crystal is measured, and computer processing of these measurement data indicates the three-dimensional spatial structure of the protein molecules that make up the crystal. In other words, the first step in the accepted way
To discover the structure of a protein molecule is the creation of crystals from that protein. But unfortunately, the envelope proteins of retroviruses do not tend to crystallize: in many cases, as soon as they are separated from the virus envelope, they disintegrate. It so happened that many attempts to create crystals from them did not go well.
Dr. Deborah Fass, in the past, was able to determine the structures of different parts of the viral envelope proteins, but in her current research, she aimed to understand how the entire complex system worked together. To achieve this goal, Dr. Fass and research student Natan Zauberman contacted scientists from the Department of Structural Biology at the Max Planck Institute in Martinsried (near Munich), Germany. Together they searched for an alternative method, "a way to bypass formation", to decipher the protein structure. They used an electron microscope, a tool normally used to look at larger structures such as cross-sections of cells. The observation of the coat protein system of the retroviruses, which is a much smaller unit than a living cell, stretched the limits of this technology. This is a method called cryo-electron tomography, which involves freezing whole viruses (retroviruses) in liquid ethane. The frozen viruses are photographed using the electron microscope at different angles, and then, using a computerized system, the three-dimensional spatial structure of the protein molecules is assembled from the various photographs.
The structure obtained in this way is characterized by a lower resolution than that which can be obtained by the conventional method of forming the proteins and irradiating the crystals with X-rays, but this resolution also provides valuable, detailed and accurate information about the proteins being studied - in their natural environment. "After years of efforts and attempts, suddenly the real structure appeared before our eyes," says Dr. Fass. "It is true that various parts and some aspects were familiar to us from the past, but there were also other parts, completely unexpected." The great difference between the systems of the retroviruses and the parallel structures of other viruses, such as the influenza virus, stood out in particular. In fact, it turned out that the protein structure of the retrovirus changes to a large and significant extent its shape and the order of its components, in the process of making contact with the cell leading to the fusion of the virus envelope with the cell membrane.
Dr. Fass was able to see how a protein component that is part of the viral structure, whose three-dimensional spatial structure she had deciphered previously, through formation, integrates into the complete viral system. The retrovirus studied in these studies is similar to the one that causes leukemia in humans. Now the scientists are planning a new series of experiments with the aim of understanding the changes that occur in the configuration of the protein system in the virus envelope, and to develop ways and methods to stop this happening. The success of this mission will mark the beginning of the development of ways and methods to curb and prevent various diseases caused by retroviruses, such as certain types of leukemia, viral hepatitis, AIDS, and more.
The bacteria and viruses know
AIDS scientist
Ydan Hassars
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