Research Article: The ribosome and its role in protein folding: looking through a magnifying glass

Date Published: June 01, 2017

Publisher: International Union of Crystallography

Author(s): Abid Javed, John Christodoulou, Lisa D. Cabrita, Elena V. Orlova.


The structural biology of co-translational protein folding on the ribosome is reviewed.

Partial Text

All proteins are synthesized on the ribosome, the universal protein-biosynthesis machinery found in all kingdoms of life. The ribosome, a ribonucleoprotein macromolecular complex (ranging in size from 2.5 to 4.5 MDa), consists of two subunits that comprise ribosomal RNA (16S for small and 23S for large subunits in bacteria, and 18S for small and 28S for large subunits in eukaryotes) and ribosomal proteins (54 in bacteria and 80 in eukaryotes) (Melnikov et al., 2012 ▸). This nanomachine decodes the genetic information present within a messenger RNA (mRNA) transcript and synthesizes a polypeptide chain. Protein translation by the ribosome can be divided into four main stages: initiation, elongation, termination and recycling (Fig. 1 ▸). The small subunit mediates base-pairing interactions between the mRNAs and tRNA that determine the correct amino-acid sequence of the nascent polypeptide chain, while the large subunit catalyses peptide-bond formation at the peptidyl transferase centre (PTC) between the amino acids covalently attached to tRNA during elongation (Schmeing & Ramakrishnan, 2009 ▸; Steitz, 2008 ▸; Moore, 2009 ▸). During protein biosynthesis, the nascent chain (NC) emerges vectorially (N-terminus emerging prior to the C-terminus) from the exit tunnel within the large subunit (Bernabeu & Lake, 1982 ▸; Milligan & Unwin, 1986 ▸; Yonath et al., 1987 ▸), where it can begin to fold in a process described as co-translational protein folding (Netzer & Hartl, 1997 ▸).

Our understanding of how proteins fold in cells is taking shape owing to remarkable developments in experimental and methodological approaches. The elucidation of the structure and function of the ribosome has come a long way through key accomplishments made by biochemical and biophysical methods, complemented by high-resolution structural tech­niques: X-ray crystallography, cryo-EM and NMR spectroscopy. The recent progress in cryo-EM and NMR has further enabled researchers to tackle structural variations in ribosomal complexes of a dynamic nature. Near-atomic structures of many functional ribosome complexes (e.g. RNCs) are beginning to illuminate the role of the ribosome beyond protein translation, which includes the translational arrest and co-translational folding processes.




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