Researchers solve longstanding mystery of protein release in cells

But scientists have long puzzled over one detail: If all it takes is a water molecule to release the finished protein, why doesn't it happen by accident?

From hard drive to 3D printer

In the cell, the ribosome and helper proteins read the "language" of nucleotides in mRNA and translate it into the "language" of amino acids in a protein.

Yury Polikanov, professor of biological sciences in the UIC College of Liberal Arts and SciencesThe ribosome is like a cellular 3D printer that actually receives the instructions from the genome and makes a protein."

The ribosome stops "printing" a new protein once it encounters a special signal in the mRNA known as a stop codon. At that point, a dedicated helper molecule called a release factor enters the ribosome and triggers the release of the finished protein from the carrier molecule holding it, called transfer RNA (tRNA).

This final step involves breaking the bond between the finished protein and the tRNA through hydrolysis, a chemical reaction with a water molecule.

Knowing when to stop "printing" a protein chain is just as important as knowing when to start, Polikanov said.

"The malfunctioning of this process can lead to pretty bad consequences," like the production of faulty or dangerous proteins, he said. For example, mutations in stop codons can lead to fatal conditions like cystic fibrosis or Duchenne muscular dystrophy.

Getting the full picture

Previously, researchers couldn't figure out exactly what was happening during this bond-breaking release process. If hydrolysis just requires water, why doesn't the bond break spontaneously from a random water molecule bouncing around?

Instead, the release factor causes the tRNA to change its shape just enough to unleash its hidden chemical potential. A small part of the tRNA reaches over and breaks the bond, releasing the finished protein from the ribosome.

"It's actually kind of nudging or kicking the substrate so that it promotes hydrolysis itself," Polikanov said.

Other UIC co-authors on the paper include Elena Aleksandrova and Egor Syroegin.

Source:

University of Illinois Chicago

Journal reference: