Page 94 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

7.5 What Mutations Tell Us About Gene Function 253

Figure 7.30 Levels of polypeptide structure. (a) Covalent and noncovalent interactions determine the structure of a polypeptide.
(b) A polypeptide’s primary (1°) structure is its amino acid sequence. (c) Localized regions form secondary (2°) structures such as α helixes
and β-pleated sheets. (d) The tertiary (3°) structure is the complete three-dimensional arrangement of a polypeptide. In this portrait of
myoglobin, the iron-containing heme group, which carries oxygen, is red, while the polypeptide itself is green.
(a) Interactions determining polypetide structure (c) 2° structures
COVALENT
Peptide = O H I Disulfide
—C—N—
I
S
NONCOVALENT I
S
I
C = O • • • • • • • H— N helix -pleated sheets
Hydrogen —O–H • • •O–C—
O = (d) 3° structure
—CH 3 H C—
3
Nonpolar CH 3
I
—CH 2 H 3 C—
–+ +–
—C–O Mg O–C—
=
O
NH 2 + – O–C—
Ionic = =
—C O
I
NH 2
I ———NH + – O–C—
3 =
O
(b) 1° structure
One amino acid
H O R 2 H O R 4 H O R 6
I + = I I H = I I = I
H N H I C C N I C C N H I C C
H C N I C C N I C C N H I C — O –
I I H = I I H = I I =
R 1 H O R 3 H O R 5 H O
N terminus C terminus Myoglobin

places constraints on how a chain can arrange itself in conditions—is known as a polypeptide’s native configura-
three-dimensional space. Because the R groups distin- tion. Various forces, including hydrogen bonds, electro-
guishing the 22 amino acids have dissimilar chemical prop- static bonds, hydrophobic interactions, and disulfide
erties, some amino acids form hydrogen bonds or bridges help stabilize the native configuration.
electrostatic bonds when brought into proximity with other It is worth repeating that primary structure—the se-
amino acids. Nonpolar amino acids, for example, may be- quence of amino acids in a polypeptide—directly deter-
come associated with each other by interactions that mines secondary and tertiary structures. The information
hide them from water in localized hydrophobic regions. As required for the chain to fold into its native configuration is
another example, two cysteine amino acids can form cova- inherent in its linear sequence of amino acids.
lent disulfide bridges (–S–S–) through the oxidation of In one example of this principle, many proteins unfold,
their –SH groups. or become denatured, when exposed to urea and mercap-
All of these interactions (Fig. 7.30a) help stabilize the toethanol or to increasing heat or pH. These treatments dis-
polypeptide in a specific three-dimensional conformation. rupt the interactions that normally stabilize the secondary
The primary structure (Fig. 7.30b) determines three- and tertiary structures. When conditions return to normal,
dimensional shape by generating secondary structure: lo- some proteins spontaneously refold into their native con-
calized regions with a characteristic geometry (Fig. 7.30c). figuration without help from other agents. No other infor-
Primary structure is also responsible for other folds and mation beyond the primary structure is needed to achieve
twists that together with the secondary structure produce the proper three-dimensional shape of such proteins.
the ultimate three-dimensional tertiary structure of You should know that some proteins are unable after
the entire polypeptide (Fig. 7.30d). Normal tertiary denaturation to refold by themselves into their correct
structure—the way a long chain of amino acids naturally tertiary structure. The proper folding of these proteins re-
folds in three-dimensional space under physiological quires other proteins called chaperones that help stabilize