Intrachain and interchain hydrogen and disulfide bonds form that influence the shape of the molecule.
7.
The triple-helix molecule is stabilized by the binding of the chaperone protein hsp47, which also prevents the premature aggregation of the trimers within the cell. The resultant molecule is procollagen.
 The folded procollagen molecules pass to the Golgi apparatus and begin to associate into small bundles. This bundling is achieved by the lateral associations between uncoiled terminals of the procollagen molecules. Free and small aggregates of procollagen molecules are packaged into secretory vesicles and transported to the cell surface.
Formation of collagen fibrils (fibrillogenesis) involves extracellular events.
 As procollagen is secreted from the cell, it is converted into a mature collagen molecule by procollagen peptidase associated with the cell membrane, which cleaves the uncoiled ends of the procollagen (Fig. 6.9).
 The aggregated collagen molecules then align together to form the final collagen fbrils in a process known as fbrillogenesis. The cell controls the orderly array of the newly formed fibrils by directing the secretory vesicles to a localized surface site for discharge. The cell simultaneously creates specialized collagen assembly sites called coves. These invaginations of the cell surface allow molecules to concentrate where assembly will
SS FIGURE 6.9 • Cleavage of the pro-collagen molecule. Illustration showing the procollagen molecule with Nand C termini. Small curved arrows in the upper part of the illustration show C-terminal where terminals are split from the propeptide procollagen molecule to form the collagen (tropocollagen) molecule.
On the C terminus of the molecule, the sugar subunit is GlcNac (N acetylglucosamine) attached to mannose (Mann). (Adapted with permission from Prockop DJ, Kivirikko
KI, Tuderman L, Guzman NA. The (1.5 nm) biosynthesis of collagen and its disorders (first of two parts). N Engl J
Med 1979;301:13–23. Copyright © 1979. Massachusetts Medical Society.
All rights reserved.)
FIGURE 6.10 • Type I collagen fbril. The type I collagen fibril contains small amounts of other collagen types such as types II, III, V, and XI. Note that the core of the fibril contains collagen types V and XI, which help initiate the assembly of the type I fibril.
occur (see Fig. 6.8). Within the cove, the collagen molecules align in rows and self-assemble longitudinally in head-to-tail fashion. They also aggregate laterally in a quarter-staggered pattern (see Fig. 6.7). The collagen molecules are then cross-linked by covalent bonds that are formed between the lysine and hydroxylysine aldehyde groups. Collagen biogenesis  results in the formation of highly organized polymers called fbrils.
Collagen fibrils often consist of more than one type of collagen.
Usually different types of fibrillar collagens assemble into fibrils composed of more than one type of collagen molecule. For example, type I collagen fbrils often contain small amounts of types II, III, V, and XI. Current studies indicate that assembly of type I collagen fibrils is proceeded by formation of a fibrillar core containing type V and type XI molecules. Subsequently, type I collagen molecules are deposited and polymerized on the surface of the fibrillar core (Fig. 6.10). In addition, small amounts of type II and III collagen molecules are incorporated into type I collagen fibrils. Collagen types V and XI are important regulators of fibrillogenesis. They control the thickness of type I fibrils by limiting the deposition of collagen molecules after the fibril has reached the desired diameter.