chapter 11
Heteropolysaccharides II: Proteoglycans and Peptidoglycans
is tryptophan (an essential amino acid). Collagen consists
essentially of four amino acids in abundant quantities and
negligible amounts of almost all other amino acids. For
this reason, collagen is an inferior protein nutritionally.
It is very insoluble in water and, for the most part, indi-
gestible. However, collagen can be converted to soluble
and digestible products by hydrolysis of some covalent
bonds (by the use of heat or by certain plant proteinases)
to yield gelatin. In the human body, collagen is resistant to
most proteinases. Polymerized fibrillar collagen is a sta-
ble component of the extracellular matrix and its turnover
rate is insignificant except in areas where tissue remodel-
ing and repair occur. However, nonfibrillar collagens (e.g.,
type IV) are susceptible to proteolytic attack. Specific pro-
teases (collagénases) cleave collagen at specific sites.
The amino acid sequence of collagen produces its
unique secondary and tertiary structures. A
molecule contains three polypeptide chains, each coiled
into a left-handed helix having about three amino acid
residues per turn (Figure 11-2). This type ofhelix is unique
to collagen and differs significantly from the a-helix in its
periodicity and dimensions (Chapter 4). The three helical
polypeptides twist tightly around each other, except for
the two short nonhelical regions at the C and N termini to
form a right handed triple-stranded superhelix. Tropocol-
lagen has a molecular weight of about 300,000, a length
of 300 nm, and a diameter of 1.5 nm. The glycine residue,
which occurs at every third position, has the smallest
R-group and is thus able to fit into the restricted space
where the three polypeptide chains are closest to each
other. Since the proline and hydroxyproline residues hin-
der free rotation around the N-C bond (Chapter 4), the
polypeptide chain has a rigid and kinked conformation.
These stereochemical properties are responsible for the
superhelix. Hydrogen bond formation between the NH
group of a glycyl residue in one chain and the CO group
of a prolyl or other amino acid residue in the X-position of
an adjacent chain stabilizes the triple helix. The hydrogen
bond between the glycyl residue of one chain and the pro-
lyl residue of another chain is direct. If the prolyl residue
is replaced by any other amino acid, the interchain hydro-
gen bond occurs through a water-bridged structure. These
bonds are further stabilized by hydrogen bonding with
the hydroxyl group of the fra«.v-4-hydroxyprolyl residue,
which occurs at the Y-position. Additionally, the chains
are held together by covalent linkages involving lysine
residues (Figure 11-3).
Polypeptide chains consisting only of glycine, proline,
and hydroxyproline residues (in that order) form an ex-
tremely stable triple helix. Furthermore, the stability (ther-
mal) of the triple helix decreases in the following order
for repeating sequences of the chain: Gly-Pro-Hyp >
Structure of tropocollagen. (a) The coiling of three left-handed helices of
collagen polypeptides. The dotted lines indicate hydrogen bonds, (b) The
right-handed triple-stranded superhelix. The curved arrow indicates the
covalent linkage between two chains. [Reproduced with permission from
I. Geis and R. E. Dickerson.]
Gly-Pro-Y > Gly-X-Pro > Gly-X-Y. In a given poly-
peptide chain of native tropocollagen, about one third of
the molecule contains the Gly-Pro-Hyp sequence and two
thirds involve Gly-X-Y, which decreases the stability of
the triple helix. Amino acid residues other than proline
and hydroxyproline that occupy the X- and Y-positions
decrease helix stability but are essential for the next level
of organization of collagen—the formation of microfibrils.
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