The side-by-side model of two tRNA molecules allowing the α-helical conformation of the nascent polypeptide during the ribosomal transpeptidation

Abstract

Lim and Spirin [25] proposed a preferable conformation of the nascent peptide during the ribosomal transpeptidation. Spirin and Lim [26] excluded the possibilities of the side-by-side model proposed by Johnson et al [13] and the three-tRNA binding model (A, P and E sites) of Rheinberger and Nierhaus [3]. However, a slight conformational change at the 3′ end regions of both A and P site tRNA molecules can enable the three different tRNA binding models to converge. With a modification of the angles of the ribose rings of both anticodon and mRNA this model can also be related to the model of Sundaralingam et al [19]. In this model of E coli rRNA the 3′ end sequence ACCA 76 or GCCA 76 of P site tRNA is base-paired to UGGU 810 of 23S rRNA, while the ACC 75 or GCC 75 of A site tRNA are base-paired to GGU 1621 23S rRNA. The conformation of the A 76 of A site tRNA is necessarily different from that of P site tRNA, at least during the course of the transpeptidation. The A 76 of A site tRNA overlaps the binding region of puromycin. The C 1400 of 16S rRNA in this model is located at a distance of 4 Å from the 5′ end of the anticodon of P site tRNA [14] and 17 Å from the 5′ end of the anticodon of A site tRNA [15]. It is also shown that a considerable but reasonable modification in the conformation of the anticodon loops could lead to accomodation of three deacylated tRNA Phe molecules at a time on 70S ribosome in the presence of poly(U) as observed experimentally [6]. A stereochemical explanation for the negatively-linked allosteric interactions between the A and E sites is also shown in the present model.