conformation, unless it is very hydrophobic. Often, such large molecules
contain a number of separate, globulardomainsof 100 or more residues.
The domains generally are connected by a single short peptide strand.
The conformation of globular proteins is often stabilized by covalent
bonds that are due toposttranslational modifications, i.e., changes occurring
during protein synthesis, but after the primary structure has formed. These
include the conjugations mentioned before, especially various glycosyla-
tions. Another modification is oxidation of the 22 SH groups of two
cysteines, forming an intramolecular 22 S 22 S 22 bridge. Figure 7.1 shows that
two 22 S 22 S 22 bridges and one free thiol group occur inb-lactoglobulin (a
fairly small globular protein). Many large globular proteins contain a great
number of sulfur bridges.
For small-molecule globular proteins and for globular domains, the
followingsize relationsroughly apply. From determinations on several of
such proteins, the volume in nm^3 equals on average 1.27M, where molar
massMis in kDa. This implies that the density of the protein then is about
1300 kg?m^3 , which is very high, comparable to the density of a crystal, and
leaving very little free space. (The interior mostly does contain some water
molecules, i.e., a few%by mass, which may be considered part of the
protein structure.) The surface area that can make contact with water is
about 9: 36 M^2 =^3 nm^2. This area is on average about 1.64 times the surface
area of a sphere of the same volume. A globular protein or domain is thus
not a perfect sphere, having an uneven surface.
It may finally be noted that the conformation of a globular protein is
not rigid: (a) Limited conformational changes often occur upon a change in
conditions, such as the binding of a ligand. (b) Vibration of molecular
segments occurs even in the core, allowing exchange of small species, e.g.,
protons, albeit slowly. In fact, a protein molecule is rather dynamic, and its
conformation represents an average. (c) As will be seen in the next section,
there will always be a proportion of the molecules, however small, in a
partly or fully unfolded state. (d) Side groups at the surface may have
considerable conformational freedom and can be reactive.
Forfibrous proteinsvery different relations hold. Most of them are
‘‘structural proteins.’’ This means that they act as construction materials, as
in silk (fibroin), tendon (collagen), blood clots (fibrin), or muscle (myosin).
These molecules have a very elongated structure, most of them containing a
high proportion ofb-sheet, and they often have a fairly regular primary
structure. The average hydrophobicity is low,< 3 :5kJ?mol^1 , and their
molar mass generally is very large. The large size is mostly due to 22 S 22 S 22
bridges and other cross-links between peptide chains, thereby producing
fibers. These posttranslational modifications also serve to stabilize the
secondary structure.
singke
(singke)
#1