Structural Aspects of Protein Synthesis

The following sections are included:

• Preface

• Contents

• List of Abbreviations

Protein synthesis is a remarkable process as the term translation indicates. The genetic information stored in the nucleic acids, RNA and DNA, expressed in a “language” of a four-letter “alphabet” and three-letter “words”, is TRANSLATED into proteins, which have a much more diverse 20-letter alphabet. The information contained in the chromosomal DNA is transcribed into messenger RNA (mRNA). Subsequently the four nucleotides (A, C, G, U) in an mRNA are translated into the 20 amino acids that make up the proteins. For this translation, there are rules like those for any written message. There is a dictionary for the translation, the genetic code, and there are signals indicating start and stop. The fact that this dictionary or genetic code is universal is a very remarkable observation. A message from one organism can normally be correctly translated by a different organism. The evolutionary aspects of this are fascinating. Not only does all life on earth appear to have a common origin. In addition, the exchange of genetic material between different organisms over the billions of years of evolution has been extensive. Thus, it is not excluded that a cow could “infect”, or transfer genetic material to, a bacterium…

There are many shorter or longer accounts of historical developments related to protein synthesis (Perutz, 1962; Nomura, 1990; Spirin, 1999; Woese, 2001; Rich, 2001; Hoagland, 2003).

A fundamental basis for protein synthesis is the realization that DNA is the genetic material. How the information flows from DNA into proteins began to be revealed about half a century ago and is reviewed in a still very enjoyable way by Watson (1964). In eukaryotic cells, the DNA is contained in the nucleus while proteins are synthesized in the cytoplasm. Several lines of observation made it clear that RNA had to be the missing link (Chamberlin & Berg, 1962). The information contained in the DNA is transmitted to an intermediate, a messenger RNA (mRNA), which subsequently can be translated into proteins (Crick, 1958). The double-helical structure of DNA (Watson & Crick, 1953) provided an insight of fundamental importance for protein synthesis in that it explained the main interactions involved in replication as well as in transcription and translation. However, what was the machinery that could perform this remarkable process?…

The following sections are included:

• LOW RESOLUTION METHODS

• HIGH RESOLUTION METHODS

The following sections are included:

• THE GENETIC CODE

• TRANSCRIPTION

• PROCESSING OF THE TRANSCRIBED RNA

• READING FRAME AND USAGE OF THE GENETIC CODE

The following sections are included:

• STRUCTURE

• tRNA CONFORMATIONS WHEN BOUND TO THE RIBOSOME

• SYNTHESIS

• CODON-ANTICODON RELATIONSHIPS

• CHARGING — THE tRNA SYNTHETASES

The following sections are included:

• THE COMPOSITION OF RIBOSOMES

• rRNA

• RIBOSOMAL PROTEINS

• THE ASSEMBLY OF RIBOSOMES

The following sections are included:

• EARLY STUDIES OF THE STRUCTURE OF RIBOSOMAL SUBUNITS AND RIBOSOMES

• CRYSTAL STRUCTURES OF RIBOSOMES

• THE STRUCTURES OF THE RIBOSOMAL RNA MOLECULES

• THE STRUCTURES OF RIBOSOMAL PROTEINS

The following sections are included:

• THE BINDING OF mRNA

• THE tRNA BINDING SITES

• THE PEPTIDYL TRANSFER CENTER (PTC)

• THE POLYPEPTIDE EXIT TUNNEL

• THE GTPASE BINDING SITE

• THE RIBOSOMAL STATES

No Abstract Available.

The following sections are included:

• THE GTPASES

• INITIATION FACTORS

• ELONGATION FACTORS

• RELEASE FACTORS

• RIBOSOME RECYCLING FACTOR (RRF)

• tRNA MIMICRY

• ADDITIONAL RIBOSOME-BINDING GTPASES

• RIBOSOME RESCUE FACTORS

The following sections are included:

• INHIBITORS OF INITIATION

• INTERFERENCE WITH DECODING. DISTORTION OF FIDELITY

• INHIBITORS OF AMINOACYL-tRNA BINDING

• INHIBITORS OF PEPTIDYL TRANSFER

• INHIBITORS OF THE EXIT TUNNEL — THE MACROLIDES

• INHIBITORS OF TRANSLOCATION

• INHIBITORS OF TRANSLATION FACTORS

The following sections are included:

• THE DYNAMICS OF TRANSLATION AND THE RIBOSOME

• CENTRAL ASSAYS

• INITIATION

• ELONGATION

• TERMINATION

• RIBOSOME RECYCLING

The following sections are included:

• FOLDING OF THE NASCENT CHAIN

• TRANSPORT OF THE PRODUCT

The following sections are included:

• EVOLUTION OF CODONS, tRNAS AND tRNA SYNTHETASES

• EVOLUTIONARY RELATIONSHIP BETWEEN tRNAS AND RIBOSOMAL RNAS

• EVOLUTIONARY RELATIONSHIP OF RIBOSOMAL PROTEINS

• THE RNA WORLD

The following sections are included:

• Appendix I

• Appendix II

• References

• Index