Domain organizations of extracellular matrix proteins and their evolution

The astonishing diversity in structure and function of extracellular matrix (ECM) proteins originates from different combinations of domains. These are defined as autonomously folding units. Many domains are similar in sequence and structure indicating common ancestry. Evolutionarily homologous domains are, however, often functionally very different, which renders function prediction from sequence difficult. Related and different domains are frequently repeated in the same or in different polypeptide chains. Common assembly domains include α-helical coiled-coil domains and collagen triple helices. Other domains have been shown to be involved in assembly to other ECM proteins or in cell binding and cell signalling. The function of most of the domains, however, remains to be elucidated. ECM proteins are rather recent `inventions', and most occur either in plants or mammals but not in both. Their creation by domain shuffling involved a number of different mechanisms at the DNA level in which introns played an important role.