Mechanisms of collagen trimer assembly

It is generally accepted that the folding of collagen triple helical domain s occur from the C-terminus toward the N-terminus by a "zipper" mechanism. The regions at the C-terminus of the triple helices must therefore play a c ritical role in the processes of chain recognition and assembly to get the proper stoichiometries and of chain registration to align the chains for th e folding of the triple helix. Examination of these regions reveals a broad diversity of structures and suggests that different mechanisms of assembly are used in the various collagen and collagen-like molecules. We review he re three different mechanisms that have recently come to light. The collect ins, a group of serum proteins containing collagen-like triple helical doma ins, are assembled through hydrophobic interactions in a triple a helix. Co llagens VIII and X, Clq and several related proteins contain homologous C-t erminal domains that are characterized by a B-pleated sheet structure. They assemble through very strong hydrophobic interactions that probably involv e an "aromatic zipper". Collagens IX, XII and XIV fibril associated collage n with interrupted triple helices (FACITs), are assembled by a mechanism in which both the C-terminal triple helix and a very short cysteine-containin g sequence are involved.