Cellular Structure, Proteins, and Metabolism
63
amino acid sequence transcribed from the mutated gene would
not be altered. On the other hand, if an amino acid code mutates
to one of the termination triplets, the translation of the mRNA
message will cease when this triplet is reached, resulting in the
synthesis of a shortened, typically nonfunctional protein.
Assume that a mutation has altered a single triplet code
in a gene, for example, alanine C—G—T changed to valine
C—A—T, so that it now codes for a protein with one differ-
ent amino acid. What effect does this mutation have upon the
cell? The answer depends upon where in the gene the mutation
has occurred. Although proteins are composed of many amino
acids, the properties of a protein often depend upon a very
small region of the total molecule, such as the binding site of an
enzyme. If the mutation does not alter the conformation of the
binding site, there may be little or no change in the protein’s
properties. On the other hand, if the mutation alters the bind-
ing site, a marked change in the protein’s properties may occur.
What effects do mutations have upon the functioning of
a cell? If a mutated, nonfunctional protein is part of a chemi-
cal reaction supplying most of a cell’s chemical energy, the loss
of the protein’s function could lead to the death of the cell. In
contrast, if the active protein were involved in the synthesis
of a particular amino acid, and if the cell could also obtain
that amino acid from the extracellular fl uid, the cell function
would not be impaired by the absence of the protein.
To generalize, a mutation may have any one of three
effects upon a cell: (1) It may cause no noticeable change in cell
function; (2) it may modify cell function, but still be compatible
with cell growth and replication; (3) it may lead to cell death.
Mutations and Evolution
Mutations contribute to the evolution of organisms. Although
most mutations result in either no change or an impairment of
cell function, a very small number may alter the activity of a pro-
tein in such a way that it is more, rather than less, active, or they
may introduce an entirely new type of protein activity into a cell.
If an organism carrying such a mutant gene is able to perform
some function more effectively than an organism lacking the
mutant gene, the organism has a better chance of reproducing
and passing on the mutant gene to its descendants. On the other
hand, if the mutation produces an organism that functions less
effectively than organisms lacking the mutation, the organism is
less likely to reproduce and pass on the mutant gene. This is the
principle of
natural selection.
Although any one mutation, if it
is able to survive in the population, may cause only a very slight
alteration in the properties of a cell, given enough time, a large
number of small changes can accumulate to produce very large
changes in the structure and function of an organism.
Protein Degradation
We have thus far emphasized protein synthesis, but the con-
centration of a particular protein in a cell at a particular time
depends not only upon its rate of synthesis but also upon its
rates of degradation and/or secretion.
Different proteins degrade at different rates. In part
this depends on the structure of the protein, with some pro-
teins having a higher affi nity for certain proteolytic enzymes
than others. A denatured (unfolded) protein is more readily
digested than a protein with an intact conformation. Proteins
can be targeted for degradation by the attachment of a small
peptide,
ubiquitin,
to the protein. This peptide directs the
protein to a protein complex known as a
proteasome,
which
unfolds the protein and breaks it down into small peptides.
Degradation is an important mechanism for confi ning the
activity of a given protein to a precise window of time.
In summary, there are many steps in the path from a
gene in DNA to a fully active protein that allow the rate of
protein synthesis or the fi nal active form of the protein to be
altered (
Table 3–3
). By controlling these steps, extracellular
or intracellular signals, as described in Chapter 5, can regulate
the total amount of a specifi c protein in a cell.
Protein Secretion
Most proteins synthesized by a cell remain in the cell, pro-
viding structure and function for the cell’s survival. Some
proteins, however, are secreted into the extracellular fl
uid,
where they act as signals to other cells or provide material for
forming the extracellular matrix. Proteins are large, charged
molecules that cannot diffuse through cell membranes. Thus,
special mechanisms are required to insert them into or move
them through membranes.
Proteins destined to be secreted from a cell or to become
integral membrane proteins are recognized during the early
stages of protein synthesis. For such proteins, the fi rst 15 to
30 amino acids that emerge from the surface of the ribosome
act as a recognition signal, known as the
signal sequence
or
signal peptide.
The signal sequence binds to a complex of proteins known
as a signal recognition particle, which temporarily inhibits fur-
ther growth of the polypeptide chain on the ribosome. The
signal recognition particle then binds to a specifi c membrane
protein on the surface of the rough endoplasmic reticulum.
Table 3–3
Factors that Alter the Amount and
Activity of Specifi c Cell Proteins
Process Altered
Mechanism of Alteration
1. Transcription of DNA
Activation or inhibition by
transcription factors
2. Splicing of RNA
Activity of enzymes in
spliceosome
3. mRNA degradation
Activity of RNAase
4. Translation of mRNA
Activity of initiating factors
on ribosomes
5. Protein degradation
Activity of proteasomes
6. Allosteric and covalent
modulation
Signal ligands, protein
kinases, and phosphatases
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