Biochemist Professor Roland Beckmann researches vital processes that take place in every cell. He examines the molecular processes in the ribosomes, the protein factories of the cells. Here, the information inscribed on the genetic material is constantly being used to synthesize thousands of molecular building blocks into proteins on the assembly line. Now, his group at the Gene Center of LMU has succeeded in using so-called cryo-electron microscopy to show how and where certain enzymes interact with ribosomes to chemically modify newly formed proteins. The researchers reconstructed this process in three dimensions. They are currently presenting this structure in the journal Nature Structural and Molecular Biology.
Changes that are essential for many cell processes
During protein synthesis, individual protein building blocks - the amino acids - are linked in the ribosome to form a chain that leaves the ribosome through a ribosomal tunnel. Certain enzymes, called N-acetyltransferases (NATs), receive the chain at the tunnel exit to chemically modify it, while at the other end it is further extended by the ribosome. The modification by NATs affects protein function and is therefore essential for many cellular processes. "Until now, it was unknown how these acetyltransferases interact with the ribosome," says co-author Dr. Birgitta Beatrix.
The researchers were now able to use cryo-electron microscopy to prove that the enzyme hangs just below the exit of the ribosomal tunnel and "can swing back and forth like a hammock," emphasizes first author and doctoral student Alexandra Knorr. It is recorded at four sites on the ribosome. It was completely surprising that three of these sites are so-called "expansion segments", so to speak flexible spacers made of ribosomal RNA, which occur only in eukaryotes. "The function of these segments has been puzzling so far. We have now assigned a function to them for the first time, "says Beatrix. Because the "expansion segments" protrude a little from the surface of the ribosome, there is a gap between the tunnel exit and the catalytic center of the acetyltransferase, which the fresh amino acid chain has to protrude by at least 20 building blocks from the tunnel end. Other enzymes can use this space to reach the growing protein chain and, in turn, chemically alter the amino acids before the protein reaches the catalytic center of the acetyltransferase. "Using our results, we were able for the first time to create a mechanistic model of how to coordinate different cellular components to modify the growing amino acid chain," says Beckmann.
Nature Structural and Molecular Biology 2018
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