The General Structure of Transfer RNA Molecules ( base stacking / hydrogen bonding / tRNA sequences / tRNA conformation )

Abstract

The three-dimensional structure of yeast phenylalanine tRNA serves as a useful basis for understanding the tertiary structure of all tRNAs. A large number of tRNA sequences have been surveyed and some general conclusions are drawn. There are only a few regions in the molecule in which there are differences in the number of nucleotides; and the structure of yeast phenylalanine tRNA can accommodate these differences by forming or enlarging protuberances on the surface of the basic framework molecule. The nature and distribution of the differences in number of nucleotides are surveyed and possible hydrogen bonding interactions are discussed for a number of tRNA classes. The two most significant features of the molecule are the large number of stacking interactions which are seen to include most of the nucleotides in the molecule and the system of specifie hydrogen bonding interactions. It is likely that these stabilizing elements are preserved in all tRNA structures. Until recently the most striking feature of transfer RNA (tRNA) sequences has been the fact that they could all be arranged in the familiar cloverleaf diagram with complementary hydrogen bonding between the bases in the stem regions (1). In addition, some positions are always occupied by constant nucleotides. Almost 2 years ago, the x-ray diffraction analysis of yeast phenylalanine tRNA (tRNAPhe) at 4-A resolution showed that this molecule not only contains the double helical stems implicit in the cloverleaf diagram, but also was found to have an L shape with the anticodon loop at one end of the L, the acceptor stem at the other end, and the dihydrouracil (D) and TVC loops forming the corner of the molecule (2). More recently the x-ray diffraction analysis of this molecule has been extended to 3resolution for both the orthorhombic (3, 4) and monoclinic crystal forms (5) and the tertiary interactions in both crystal forms appear very similar. The most striking feature of the 3-A analysis is the extent to which a large number of the bases which are constant to all tRNAs are used in the tertiary hydrogen bonding interactions. These, together with -base stacking, maintain the threedimensional form of the molecule. This suggests rather directly that the three-dimensional structure seen in yeast tRNAPhe may be generalized to understand the structure of all tRNAs. The idea that all tRNAs have a common or similar structure is not surprising in view of the fact that all tRNAs involved in protein synthesis must go through the ribosomal machinery. Here we discuss the manner in which the three-dimensional structure of yeast tRNAPhe may serve as a framework for understanding the structure of all tRNA molecules. We do this by comparing tRNA sequences (6) and suggesting plausible ways in which structural components in this molecule may be modified to fit in other tRNA sequences. Structural features of yeast phenylalanine tRNA The preliminary details of yeast tRNAPhe tertiary interactions have been published (4, 5). Further improvement of the phases using a "partial structure method" (Sussman and Kim, in preparation) has reinforced most of the tertiary interactions previously published and reveals more clearly regions which were previously uncertain (manuscript in preparation). Fig. 1 shows the familiar cloverleaf sequence for yeast tRNAPhe (7), and the solid lines indicate tertiary hydrogen bonding interactions. In addition, positions occupied by constant bases are indicated. It can be seen that many of the tertiary hydrogen bonding interactions involve nucleotides which are constant in all tRNA sequences. The three-dimensional form of the molecule is shown schematically in Fig. 2 in which -the ribose-phosphate backbone is represented as a continuous tube and the rodlike crossbars indicate secondary interactions while the black bars represent tertiary interactions. In addition, the dotted lengths on the backbone represent regions in which there are a variable number of nucleotides in other J CONSTANT A NUCLEOTIDE E]ACCEPTOR D CONSTANT PURINE pG C STEM OR PYRIMIDINE C a G G * C70 G ° U A5 A TU C LOOP U A

6 Figures and Tables

Cite this paper

@inproceedings{SuddathTheGS, title={The General Structure of Transfer RNA Molecules ( base stacking / hydrogen bonding / tRNA sequences / tRNA conformation )}, author={F L Suddath and G. J. Quigley and Anne McPherson and Andrew H.- J. Wang and Nadrian C. Seeman} }