In a breakthrough that could lead to new treatments for diseases like Alzheimer's and cancer, researchers have solved the mystery of how cells unfold proteins.
The study, published in the journal Nature, reveals the atomic-level details of how a molecular machine called the ribosome unfolds proteins as they are being made. This process, known as protein translocation, is essential for the proper function of cells.
"This is a major milestone in our understanding of how cells work," said study leader Dr. James Bardwell, a professor of biochemistry and molecular biology at the University of California, Berkeley. "We now have a clear picture of how the ribosome unfolds proteins, which could lead to new ways to treat diseases that are caused by protein misfolding."
Protein misfolding is a common problem in cells. It can occur when proteins are exposed to heat, chemicals, or other stressors. Misfolded proteins can clump together and form aggregates, which can damage cells and lead to disease.
In Alzheimer's disease, for example, misfolded proteins called amyloid-beta and tau form aggregates in the brain that are thought to contribute to the development of the disease. In cancer, misfolded proteins can promote the growth and spread of tumors.
The ribosome is a large molecular machine that is responsible for synthesizing proteins. It reads the genetic code in messenger RNA (mRNA) and uses this information to assemble amino acids into proteins.
As the ribosome synthesizes a protein, it also unfolds the protein so that it can be properly folded into its functional shape. This process is essential for the protein to function properly.
The new study reveals the atomic-level details of how the ribosome unfolds proteins. The researchers used a technique called cryo-electron microscopy to visualize the ribosome in action. This technique allowed them to see the ribosome in unprecedented detail, which enabled them to determine how it unfolds proteins.
The findings of the study could lead to new ways to treat diseases that are caused by protein misfolding. By understanding how the ribosome unfolds proteins, researchers may be able to develop drugs that can prevent proteins from misfolding or that can help cells to clear away misfolded proteins.
"This study is a major breakthrough in our understanding of how cells work," said Bardwell. "We are excited about the potential implications of this research for the treatment of diseases like Alzheimer's and cancer."