Electrostatic Interactions Govern Extreme Nascent Protein Ejection Times from Ribosomes and Can Delay Ribosome Recycling.

Journal of the American Chemical Society
Daniel A NissleyEdward P O'Brien

Abstract

The ejection of nascent proteins out of the ribosome exit tunnel, after their covalent bond to transfer-RNA has been broken, has not been experimentally studied due to challenges in sample preparation. Here, we investigate this process using a combination of multiscale modeling, ribosome profiling, and gene ontology analyses. Simulating the ejection of a representative set of 122 E. coli proteins we find a greater than 1000-fold variation in ejection times. Nascent proteins enriched in negatively charged residues near their C-terminus eject the fastest, while nascent chains enriched in positively charged residues tend to eject much more slowly. More work is required to pull slowly ejecting proteins out of the exit tunnel than quickly ejecting proteins, according to all-atom simulations. An energetic decomposition reveals, for slowly ejecting proteins, that this is due to the strong attractive electrostatic interactions between the nascent chain and the negatively charged ribosomal-RNA lining the exit tunnel, and for quickly ejecting proteins, it is due to their repulsive electrostatic interactions with the exit tunnel. Ribosome profiling data from E. coli reveals that the presence of slowly ejecting sequences correlates with ri...Continue Reading

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Citations

Sep 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Frédéric PoitevinKhanh Dao Duc
Aug 17, 2020·The Biochemical Journal·Rodrigo D RequiãoFernando L Palhano
Mar 29, 2021·The Journal of Biological Chemistry·Géssica C BarrosFernando L Palhano
Jun 25, 2021·The Journal of Physical Chemistry. B·Yang Jiang, Edward P O'Brien
Jun 25, 2021·Frontiers in Molecular Biosciences·Mateusz Chwastyk, Marek Cieplak
Aug 14, 2020·The Journal of Physical Chemistry. B·Hoang Linh NguyenMai Suan Li
Sep 24, 2021·Biophysical Journal·Phuong Thuy Bui, Trinh Xuan Hoang

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