Form follows function: structure of an elongation factor G-ribosome complex.

Abstract

Not so long ago, the idea of deriving functional models from just looking at large subcellular structures in different functional states seemed unrealistic. In the meantime, the visualization of such structures by three-dimensional reconstructions from cryoelectron microscopic images has made enormous progress. Studies on ribosomes, from both prokaryotes and eukaryotes, have been particularly rewarding. The structure of the Escherichia coli ribosome was determined at ≈25-A resolution in 1995 by the groups of Frank (1) and van Heel (2) and was improved to 18 A recently (3). Likewise, reconstructions of eukaryotic ribosomes have been obtained recently (4–6). Regarding functional complexes, it was possible to localize tRNA molecules in three binding sites (A, P, and E) on the E. coli ribosome (7) and to determine their respective pre- and post-translocation positions (8). The complex of elongation factor (EF) Tu with Phe-tRNA was visualized in the ribosomal A site at 18-A resolution (3), and, by fitting the crystal structure of the complex (9), the structure could be interpreted in terms of specific interactions with the ribosome. Another recent reconstruction visualized at the protein exit site of the eukaryotic ribosome a protein complex, Sec 61, that is involved in cotranslational protein translocation through the membrane of the endoplasmic reticulum (4). The paper by Agrawal et al. (10) in a recent issue of the Proceedings reports the structure of another important functional ribosomal complex that is a complex of EF-G with E. coli ribosomes. The structure represents a late state of the translocation reaction in the ribosomal elongation cycle. Translocation is catalyzed by EF-G at the expense of GTP and consists of the coordinated movement of two mRNA-bound tRNAs from their pretranslocational positions to their post-translocation positions. The present reconstruction has a resolution of 20 A and clearly shows the factor, a …