Proline is an amino acid with a unique cyclic structure that facilitates the folding of many proteins, but also impedes the rate of peptide bond formation by the ribosome. As a ribosome substrate, proline reacts markedly slower when compared with other amino acids both as a donor and as an acceptor of the nascent peptide. Furthermore, synthesis of peptides with consecutive proline residues triggers ribosome stalling. Here, we report crystal structures of the eukaryotic ribosome bound to analogs of mono‐ and diprolyl‐tRNAs. These structures provide a high‐resolution insight into unique properties of proline as a ribosome substrate. They show that the cyclic structure of proline residue prevents proline positioning in the amino acid binding pocket and affects the nascent peptide chain position in the ribosomal peptide exit tunnel. These observations extend current knowledge of the protein synthesis mechanism. They also revise an old dogma that amino acids bind the ribosomal active site in a uniform way by showing that proline has a binding mode distinct from other amino acids.
Proline impedes the rate of peptide bond formation or induces ribosome stalling. Structures of the eukaryotic ribosome bound to prolyl‐ and diprolyl‐tRNA analogs reveal a unique binding mode of proline and how this impacts peptide synthesis.
Crystal structures of the eukaryotic ribosome show accommodation of proline residues in two active sites of the ribosome: the catalytic center and the nascent peptide tunnel.
The rigid chemical structure of proline prevents its optimal positioning in both of the active sites.
- Received June 23, 2016.
- Revision received September 28, 2016.
- Accepted September 30, 2016.
- © 2016 The Authors