Ribosomes are composed of two conserved subunits

The ribosome is the large macromolecular machine responsible for translation of the genetic
code from nucleic acid into protein. It ranges in mass from 2.5 million daltons in bacteria to
more than 4 million daltons in eukaryotic cells. In both cases approximately two-thirds of this
mass is RNA and about one-third is protein. The RNA component is important not only in its
relative contribution to the mass of the ribosome: it also plays the central part in its function.
The ribosome is thus one of a growing number of macromolecular machines known to have
essential RNA components widely thought to reflect the early evolution of life in an RNA
world. Not surprisingly, given their fundamental role in the decoding of genetic information,
ribosomes are highly conserved both in structure and in function.
Ribosomes were first identified as large macromolecular complexes before their function was
established, and were termed the 70S particle (in the case of bacterial ribosomes) and the 80S
particle (in the case of eukaryotic ribosomes) at a time when all that was known about them
was the speed at which they sedimented in the ultracentrifuge: “S” stands for Svedberg, a unit
of sedimentation velocity. This terminology is still used for the different components of the
ribosome and sometimes for the ribosome itself and its subunits (Figure 11-3.1).
All ribosomes are composed of two subunits (Figure 11-3.1): a small subunit that mediates
the decoding interaction between the mRNA codon and the tRNA anticodon, and a large
subunit that catalyzes peptide bond formation. These distinct events are integrated at the
subunit interface of the ribosome where the tRNA substrates bind (Figure 11-3.2). To
sequentially add amino acids to a growing polypeptide chain, the ribosome undergoes gross
movements that shift the position of the tRNA-mRNA complex. These movements, termed
translocation, occur at the subunit interface and must be coordinated by the RNA-RNA,
RNA-protein and protein-protein bridges between the large and small subunits. The
mechanism by which these interactions between the large and the small subunit contribute to
the decoding of the mRNA is described in the next sections, where we shall see that the
crucial part played by the rRNAs is reflected in their remarkably conserved secondary and
tertiary structure. Certain nucleotide stretches in the rRNAs are conserved across all species:
for example 16 of 17 contiguous nucleotides in 16S rRNA are more than 95% conserved
across the three kingdoms of life. Some ribosomal proteins also are highly conserved, and
these probably are those most critical to ribosome function; other ribosomal proteins are not
present in all species.
Protein and RNA are differentially distributed on the exterior and
interface surfaces of the ribosome
Atomic structures of both the small and the large subunits of the ribosome have been
obtained by X-ray crystallography and help us to understand how the different components
contribute to its central functions. The interface between the small and large subunits of the
ribosome is rich in ribosomal RNA (rRNA) elements and relatively poor in ribosomal
proteins (Figure 11-3.2). On the exterior (solvent) side of the particle, ribosomal proteins are
more evenly distributed. A number of the ribosomal proteins have unusual structures,
consisting of globular domains embedded in the exterior face of the particle with long
extended arms that snake their way into the core of the rRNA structure. These arms are
generally enriched in basic amino acids and are thought to act as mortar in packing the
negatively charged rRNA phosphate backbone into a compact tertiary structure.
Biochemical and genetic evidence long pointed to a critical role for rRNA in translation. The
crystal structures of both ribosomal subunits confirm that rRNA is the primary component in
the functional centers at the interface of the ribosomal subunits where the tRNA substrates
bind and interact (Figure 11-3.2). Binding of model tRNA substrates (that represent the
CCAends of the aminoacylated tRNAs) to the large ribosomal subunit crystals identified the
active site for peptide bond formation. There are no protein elements within 18 Å of the
region where peptide bond formation must occur. Thus, the ribosome is a ribozyme providing
critical evidence for the existence of an RNA world early in evolution.

rRNA organization in the two subunits is distinct

The large rRNAs from the two ribosomal subunits can be subdivided into distinct regions, or
domains, based on their secondary structures. The l6S (or 18S in eukaryotes) rRNA is
divided into three major and one minor domain whereas the 23S (or 28S) rRNA is divided
into 6 different domains. The organization of the rRNA domains in the two subunits is
strikingly different. In the small subunit, each rRNA domain is largely limited to one area of
the subunit: the body, the platform, the head, or the penultimate stem. In contrast, the rRNA
elements in the large subunit are intricately interwoven (Figure 11-3.3). It has been suggested
that this organization reflects the functional differences of the subunits: interdomain
flexibility is suited to the large scale movements of translocation performed by the small
subunit whereas stability provided by the interwoven RNA domains is suited to protection of
the active site by the large subunit.