Inside tiny cellular machines called ribosomes, chains of genetic material called messenger RNAs (mRNAs) are matched with the corresponding transfer RNAs (tRNAs) to create sequences of amino acids that exit the ribosome as proteins. Unfinished proteins are called nascent chainsm and they are left attached to the ribosome.
Scientists know that some of these nascent chains can regulate the activity of the ribosome and that the nascent chains can sometimes interfere with antibiotics — many of which work by targeting bacterial ribosome activity. Scientists do not know why this happens, mainly because it is hard to visualize what the ribosome-peptide-drug interactions look like while the unfinished proteins are still tethered to the ribosome.
Now, scientists at the University of Illinois Chicago are the first to report a method for stable attachment of peptides to tRNAs, which has allowed them to gain new fundamental insights into ribosome function by determining the atomic-level structures of ribosomes and the shapes that these peptides take inside the ribosome.
Their method is newly reported in the journal Nature Chemistry.
“The challenge has been to see up close the structure of the ribosome and the exit tunnel in the presence of the nascent peptides because, in nature, the ribosome is very quick for us to capture images or conduct experiments,” said Yury Polikanov, associate professor in the biological sciences department at the College of Liberal Arts and Sciences. “Until the advent of this new method, we’ve essentially been blinded from seeing what is happening in the active site of the ribosome at this critical moment in time.”
Polikanov and his colleague Egor Syroegin, a PhD candidate in biological sciences at UIC, used a method called native chemical ligation to fuse custom peptides with the tRNA to yield what is called a peptidyl-tRNA.
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