Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

338 Chapter 6: How Cells Read the Genome: From DNA to Protein
(A)
H
O
aminoacyltRNA
C
C
O
NH 2
R
(B)
O
NH 2
_ O P O N
C C N
O HC
C CH
5′ N
CH N
2
O
3′ 2′
O OH
O
C
H C R amino acid
NH 2
which one amino acid (cysteine) was chemically converted into a different amino
acid (alanine) after it already had been attached to its specific tRNA. When such
“hybrid” aminoacyl-tRNA molecules were used for protein synthesis in a cell-free
system, the wrong amino acid was inserted at every point in the protein chain
where that tRNA was used. Although, as we shall see, cells have several quality
control mechanisms to avoid this type of mishap, the experiment did establish
that the genetic code is translated by two sets of adaptors that act sequentially.
Each matches one molecular surface to another with great specificity, and it is
their combined action that associates each sequence of three nucleotides in the
mRNA molecule—that is, each codon—with its particular amino acid.
Figure 6–55 The structure of the
aminoacyl-tRNA linkage. The carboxyl
end of the amino acid forms an ester
bond to ribose. Because the hydrolysis of
this ester bond is associated with a large
favorable change in free energy, an amino
acid held in this way is said to be activated.
(A) Schematic drawing of the structure. The
amino acid is linked to the nucleotide at
the 3ʹ end of the tRNA (see Figure 6–50).
(B) Actual structure corresponding to the
boxed region in (A). There are two major
classes of synthetase enzymes: one links
the amino acid directly to the 3ʹ-OH group
of the ribose, and the other links it initially
to the 2ʹ-OH group. In the latter case, a
subsequent transesterification reaction
shifts the amino acid to the 3ʹ position.
As in Figure 6–54, the “R group” indicates
the side chain of the amino acid.
Editing by tRNA Synthetases MBoC6 Ensures m6.57/6.55 Accuracy
Several mechanisms working together ensure that an aminoacyl-tRNA synthetase
links the correct amino acid to each tRNA. Most synthetase enzymes select
the correct amino acid by a two-step mechanism. The correct amino acid has
the highest affinity for the active-site pocket of its synthetase and is therefore
favored over the other 19; in particular, amino acids larger than the correct one
are excluded from the active site. However, accurate discrimination between two
similar amino acids, such as isoleucine and valine (which differ by only a methyl
amino acid
(tryptophan)
H
H 2 N C C
CH 2
O
OH
tRNA
(tRNA Trp )
H 2 N
H
C
CH 2
C
O
O
high-energy
bond
H 2 N
H
C
CH 2
C
O
O
C
C
C
N CH
H
N CH
H
N CH
H
ATP
AMP
tRNA synthetase
(tryptophanyl
tRNA synthetase)
A C C
linkage of amino acid
to tRNA
A C C
tRNA binds to its
codon in RNA
+ 2P i
U G G
3′ A C C 5′
base-pairing
5′ 3′
mRNA
NET RESULT: AMINO ACID IS
SELECTED BY ITS CODON
Figure 6–56 The genetic code is translated by means of two adaptors that act one after another. The first adaptor is the aminoacyl-tRNA
synthetase, which couples a particular amino acid to its corresponding tRNA; the second adaptor is the tRNA molecule itself, whose anticodon
forms base pairs with the appropriate codon on the mRNA. An error in either step would cause the wrong amino acid to be incorporated into a
protein chain (Movie 6.6). In the sequence of events shown, the amino acid tryptophan (Trp) is selected by the codon UGG on the mRNA.