An
Introduction to
Ribosome Structure
David Marcey
©2003
I.
Introduction
Ribosomes are the large,
ribonucleoprotein factories in which proteins are synthesized. In this process,
messenger RNA (mRNA) codons are read by the anticodons of adaptor, transfer
RNAs (tRNAs) that carry codon-specific amino acids. These amino acids are
added to a growing protein chain by peptide bond formation in the heart of
the ribosome.
The massive, macromolecular
assemblage at left is the crystal structure of the 70S ribosome from Thermus
thermophilus, a highly thermophilic bacteria first discovered
in deep-sea hot vents.The structure contains 42
proteins and 3 ribosomal RNAs
(rRNA).
reset molecule
return
to beginning of exhibit
II. Subunit Structure
The 70S ribosome comprises two subunits: a large 50S
subunit, and a small 30S subunit.
The 50S subunit contains a 23S
and a 5S rRNA plus over 30
proteins, 22 of which are resolved in the
structure in the left frame. The 30S subunit contains
a 16S rRNA plus 20 proteins.
The positions and conformations of the rRNA components of each subunit can be
visualized as follows:
- The 16S rRNA
of the small, 30S subunit folds into four domains: 5',
central, 3' major,
and 3' minor. The structural autonomy of these
domains implies that they move relative to one another during protein synthesis.
- The 23S rRNA
of the large, 50S subunit folds into six secondary structural domains containing
over 130 RNA helices: I, II,
III, IV, V,
VI. These six domains, unlike those of the 16S
rRNA of the small subunit, are thoroughly intertwined.
The 5S rRNA forms
a seventh domain of rRNA tertiary structure in the large subunit.
reset molecule
return
to beginning of exhibit
III. tRNA Binding and Codon Recognition
The ribosome
binds 3 tRNAs, each in a distinctive binding site
made from structural elements contributed by both the 50S
subunit and the 30S
subunit.
The A-site
tRNA, P-site tRNA, and E-site
tRNA exhibit slight conformational differences. However, all adopt the
classical "L shape" tertiary structure. Their 3' ends (which are bound
by the 50S subunit and which attach to amino acids and peptides through an acyl
bond) point down, and their anticodon stem-loops point into the 30S
subunit in the view at left.
Note the
tight juxtaposition of the 3' ends of the A-site
and P-site tRNAs
in the peptidyl transferase site of the 50S subunit (not shown). The A-site
tRNA bears an incoming amino acid (not shown),
and the P-site
tRNA carries the growing peptide chain (not shown).
Peptide bond formation attaches the peptide to the A-site
tRNA's amino acid. The P-site
tRNA then moves to the E-site
(E stands for "exit"), replacing the former, uncharged E-site
tRNA. The A-site
tRNA, now bearing the growing peptide, is shifted into the P
position. A new tRNA bearing the next amino acid is then brought into
the A-site.
Turning now
to codon recognition, it can be seen that the 30S
subunit binds the anticodon stem loops of the tRNAs
as well as the mRNA being translated (two, triplet
codons are shown).
The A-site
and P-site tRNAs
(phe-tRNAs in the structure shown at left) bear the anticodon residues (AAG)
that hydrogen bond with the two UUU codons of the mRNA:
The G-U bonding in third
position of each codon is an example of "wobble" base pairing. Wobble
pairing allows some codons that differ in the third, 3' base to be recognized
by the same tRNA anticodon. This, together with examples of isoaccepting tRNAs
that carry the same amino acid but whose anticodons differ in the wobble base,
allows for the high degree of degeneracy found in the genetic code.
The distance between the 5'G of the P-site
anticodon and the 3'A of the A-site anticodon is
~14 Angstroms. In order to accommodate simultaneous base pairing of both A-
and P-site codons and anticodons, the mRNA backbone
is observed to adopt a significant kink.
reset molecule
return
to beginning of exhibit
IV. References
Yusupov, M. M., Yusupova,
G. Z., Baucom, A., Lieberman, K., Earnest, T. N., Cate, J. H. D., Noller, H.
F.: Crystal Structure of the Ribosome at 5.5 A Resolution. Science 292:883-896
(2001).
return
to beginning of exhibit