The ribosome can discriminate the chirality of amino acids within its peptidyl-transferase center

Michael T. Englander, Joshua L. Avins, Rachel C. Fleisher, Bo Liu, Philip R. Effraim, Jiangning Wang, Klaus Schulten, Thomas S. Leyh, Ruben L. Gonzalez Jr., and Virginia W. Cornish
PNAS May 12, 2015 112 (19) 6038-6043; first published April 27, 2015 https://doi.org/10.1073/pnas.1424712112

  1. Edited by Ignacio Tinoco, Jr., University of California, Berkeley, CA, and approved March 24, 2015 (received for review January 8, 2015)

 

The cellular translational machinery (TM) synthesizes proteins using exclusively L- or achiral aminoacyl-tRNAs (aa-tRNAs), despite the presence of D-amino acids in nature and their ability to be aminoacylated onto tRNAs by aa-tRNA synthetases.

Although the ribosome catalyzes protein synthesis using more than 20 chemically diverse natural amino acids, these natural amino acids are all of L- or achiral configurations. As a consequence, the ability of the ribosome to incorporate L-aminoacyl-tRNAs (L-aa-tRNAs) with both a high degree of speed and accuracy has been the focus of decades of intense mechanistic and structural investigations

Our results reveal a novel mechanism through which D-aa-tRNAs interfere with translation, provide insight into how the TM might be engineered to use D-aa-tRNAs, and increase our understanding of the physiological role of a widely distributed enzyme that clears D-aa-tRNAs from cells.

engineering applications that seek to use the synthetic power of the ribosome to create novel polymers

The mechanistic insights gained from our biochemical and computational studies may help guide future efforts to engineer the TM so as to…