Protein Synthesis and Secretion as Seen by the Nascent Protein Chain

Abstract

One of the features that distinguishes the ribosome from most other enzymes is the need to retain the product of each transpeptidation reaction, specifically the nascent or growing polypeptide chain, until the mRNA-dependent polymerization of amino acids is terminated by a stop codon. Since many proteins are more than 1000 amino acids in length, the space occupied by the nascent chain attached to the ribosome-bound peptidyl-tRNA can be substantial. The ribosome must therefore be designed to minimize the interference between the growing nascent chain and the molecular traffic associated with decoding and protein chain elongation (tRNA and elongation factors). The probable solution to this structural issue was provided by Malkin and Rich (1967) and by Blobel and Sabatini (1970), who found that the ribosome protected the C-terminal 40 or so amino acids of the nascent chain from proteolytic digestion. This suggested that the nascent chain was not exposed to the cytoplasm near the peptidyltransferase center, but instead left the ribosome far from its active site. This model was later supported by immunoelectron microscopy data that detected nascent chain folding outside the ribosome at the base of the large ribosomal subunit (Bernabeu and Lake, 1982) and by x-ray diffraction data that revealed a region of low electron density in the large ribosomal subunit that extended approximately from its base to the peptidyltransferase center located near the base of the central protuberance (Yonath et al., 1987).