Protein Synthesis
Free 70S ribosome
30S subunit +- 50S subunit
FIGURE 25-14
The steps of termination of protein synthesis.
Role of GTP
GTP, like ATP, is an energy-rich molecule. Generally,
when such molecules are hydrolyzed, the free energy of
hydrolysis is used to drive reactions that otherwise are
energetically unfavorable. This does not seem to be the
case in protein synthesis. The reaction sequence indicates
that GTP facilitates binding of protein factors either to
tRNA or to the ribosome. Furthermore, hydrolysis of GTP
to GDP always precedes dissociation of the bound fac-
tor. Comparison of the structure of the free factor and the
factor-GTP complex indicates that the factor undergoes a
slight change in conformation when GTP is bound. The
function of GTP is to induce a conformational change in
a macromolecule by binding to it. Since it is easily hy-
drolyzed by various GTPases, the use of GTP as a con-
trolling element allows cyclic variation in macromolecular
shape. When GTP is bound, the macromolecule has an ac-
tive conformation, and when the GTP is hydrolyzed or re-
moved, the molecule resumes its inactive form. GTP plays
a similar role in hormone activation systems (Chapter 30).
Posttranslational Modification of Proteins
The protein molecule ultimately needed by a cell often dif-
fers from the polypeptide chain synthesized. Modification
of the synthesized chain occurs in several ways:
1. In prokaryotes, fMet is never retained as the NH2,
terminal amino acid. In roughly half of all proteins,
the formyl group is removed by the enzyme
deformylase, leaving methionine as the NH
amino acid. In both prokaryotes and eukaryotes, the
fMet, methionine, and possibly a few more amino
acids, are often removed; their removal is catalyzed
by a hydrolytic enzyme called aminopeptidase. This
hydrolysis may occur as the chain is being
synthesized or after the chain is released from the
ribosome. The choice of deformylation versus
removal of fMet usually depends on the identity of the
adjacent amino acids. Deformylation predominates if
the second amino acid is arginine, asparagine, aspartic
acid, glutamic acid, isoleucine, or lysine, whereas
fMet is usually removed if the adjacent amino acid is
alanine, glycine, proline, threonine, or valine.
2. Newly created NH
terminal amino acids are
sometimes acetylated, and amino acid side chains
may also be modified. For example, in collagen a
large fraction of the prolines and lysines are
hydroxylated (see below). Phosphorylation of serine,
tyrosine, and threonine occurs in many organisms.
Various sugars may be attached to the free hydroxyl
group of serine or threonine to form glycoproteins.
Finally, a variety of prosthetic groups such as heme
and biotin are covalently attached to some proteins.
3. Two distant sulfhydryl groups in two cysteines may
be oxidized to form a disulfide bond.
4. Polypeptide chains may be cleaved at specific sites.
For instance, chymotrypsinogen is converted to the
digestive enzyme chymotrypsin by removal of four
amino acids from two different sites. In some cases,
the uncleaved chain represents a storage form of the
protein that can be cleaved to generate the active
protein when needed. This is true of many
mammalian digestive enzymes, e.g., pepsin is formed
by cleavage of pepsinogen. An interesting precursor
is a huge protein synthesized in animal cells infected
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