A Crystallographic Analysis of Yeast Initiator tRNA

Abstract

The initiation step in the complex process of protein synthesis always begins with the incorporation of a methionine residue at the amino terminal of the growing protein chain (for review, see Grunberg-Manago and Gros 1977). A specific methionine-accepting initiator tRNA that is excluded from the elongation steps on the ribosome is the unique adaptor for the “start” signals in mRNA. Together with initiation factors and GTP, the methionylated initiator tRNA is aligned in the correct frame on the ribosome so that the first peptide bond can be formed with the first aminoacylated elongator tRNA on the A site of the ribosome.

Our understanding of the molecular structure-function relationships in initiator tRNA comes from an evaluation of a diversity of experimental results. There are the characteristic sequence patterns that have emerged from a careful examination of a great many primary structures of both initiator and elongator tRNAs (Barrell and Clark 1974; Sprinzl et al. 1978). Added to this are the variety of biochemical and biophysical studies of tRNA that have described the dynamics of molecular response to environmental perturbants (for review, see Sigler 1975; Kim 1976; Rich and RajBhandary 1976). Another very important constraint on the structure-function relationships in initiator tRNA is the detailed high-resolution structure of the elongator tRNA, yeast tRNA^Phe (Quigley et al. 1975; Jack et al. 1976; Stout et al. 1976; Sussman and Kim 1976; Holbrook et al. 1978), which is known to bear many structural similarities and even functional similarities outside the ribosome. Reported here is a...