Dr. Jin's lab solves atomic structure of stalled ribosome by cryoEM

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Prof. Hong Jin, Department of Biochemistry and Center for Biophysics and Quantitative Biology, and Dr. Fuxing Zeng, postdoctoral fellow in Jin’s laboratory. The structure is used to understand how stalled ribosomes are rescued in the cell.

This is the first atomic structure of a ribosomal complex solved by cryoEM on the U of I campus.

At a molecular level, a single ribosome is massive, containing more than half million of atoms. By contrast, a glucose molecule has 24 atoms and a water molecule contains only 3 atoms.

“It’s breathtaking to see each and every atom in this beautiful molecular machine arranged in three-dimension,” said Dr. Jin, an Assistant Professor of Biochemistry.

The ribosome, a molecular machine, produces every single protein in a living cell. Occasionally this machine is stalled, and there is a delay in the production of proteins. When protein production is stalled, it is not only problematic for the cell; it can be lethal. In human brain cells, ribosome stalling causes neurodegenerative disease.

Using the 3D atomic structure and biochemistry, Jin, postdoctoral contributor Fuxing Zeng, and Yanbo Chen, an undergraduate researcher in the Jin lab, were able to decipher how protein alternative rescue factor A (ArfA) recognizes a stalled bacterial ribosome and recruits release factor RF2 to catalyze peptide release, a process that leads to rescuing the stalled ribosome in bacterial cell.

Since bacterial and human cells employ completely different strategies to rescue stalled ribosomes, the rescue mechanism of bacteria is a drug target.

The NIH Center for Macromolecular Modeling and Bioinformatics provided critical computing resources for Dr. Jin’s team to solve the cryo-EM structure. The Center, located at the Beckman Institute, is led by Professor Emad Tajkhorshid. Dr. James C. Phillips, Senior Research Programmer and Mrinal Shekhar, a graduate student in the Tajkhorshid lab at the Beckman Institute also provided invaluable assistance.

The findings were published in Nature in January 2017.

Read the full article here.

Posted February 23, 2017.