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

THE SHAPE AND STRUCTURE OF PROTEINS
127
cysteine
C
CH 2
SH
SH
CH 2
C
C
CH 2
SH
SH
CH 2
C
OXIDATION
REDUCTION
C
CH 2
S
S
CH 2
C
C
CH 2
S
S
CH 2
C
intrachain
disulfide
bond
interchain
disulfide
bond
Figure 3–25 Disulfide bonds. Covalent
disulfide bonds form between adjacent
cysteine side chains. These crosslinkages
can join either two parts of the
same polypeptide chain or two different
polypeptide chains. Since the energy
required to break one covalent bond is
much larger than the energy required to
break even a whole set of noncovalent
bonds (see Table 2–1, p. 45), a disulfide
bond can have a major stabilizing effect on
a protein (Movie 3.7).
Covalent Cross-Linkages Stabilize Extracellular Proteins
Many protein molecules are either attached to the outside of a cell’s plasma membrane
or secreted as part of the extracellular matrix. All such proteins are directly
MBoC6 e4.26/3.24
exposed to extracellular conditions. To help maintain their structures, the polypeptide
chains in such proteins are often stabilized by covalent cross-linkages.
These linkages can either tie together two amino acids in the same protein, or
connect different polypeptide chains in a multisubunit protein. Although many
other types exist, the most common cross-linkages in proteins are covalent sulfur–
sulfur bonds. These disulfide bonds (also called S–S bonds) form as cells prepare
newly synthesized proteins for export. As described in Chapter 12, their formation
is catalyzed in the endoplasmic reticulum by an enzyme that links together two
pairs of –SH groups of cysteine side chains that are adjacent in the folded protein
(Figure 3–25). Disulfide bonds do not change the conformation of a protein but
instead act as atomic staples to reinforce its most favored conformation. For example,
lysozyme—an enzyme in tears that dissolves bacterial cell walls—retains its
antibacterial activity for a long time because it is stabilized by such cross-linkages.
Disulfide bonds generally fail to form in the cytosol, where a high concentration
of reducing agents converts S–S bonds back to cysteine –SH groups. Apparently,
proteins do not require this type of reinforcement in the relatively mild environment
inside the cell.
Protein Molecules Often Serve as Subunits for the Assembly of
Large Structures
The same principles that enable a protein molecule to associate with itself to form
rings or a long filament also operate to generate much larger structures formed
from a set of different macromolecules, such as enzyme complexes, ribosomes,
viruses, and membranes. These large objects are not made as single, giant, covalently
linked molecules. Instead they are formed by the noncovalent assembly of
many separately manufactured molecules, which serve as the subunits of the final
structure.
The use of smaller subunits to build larger structures has several advantages:
1. A large structure built from one or a few repeating smaller subunits requires
only a small amount of genetic information.
2. Both assembly and disassembly can be readily controlled reversible processes,
because the subunits associate through multiple bonds of relatively
low energy.
3. Errors in the synthesis of the structure can be more easily avoided, since
correction mechanisms can operate during the course of assembly to
exclude malformed subunits.