Protein Suicide Example: Osteogenesis imperfecta
Collagen, the most abundant human structural protein, is assembled from three polypeptide chains into a triple helical protein. The precursor molecule is then modified by removal of the globular N- and C- terminal ends and modification of some of the amino acids by hydroxylation. At least 18 different types of collagen have been identified in human tissues.
Type I collagen is made up of two 
1(I) chains and one 2(I) chain. Thus, prior to assembly, there are twice as many 1(I) chains present as depicted in the animation above by the red lines as there are 2(I) chains depicted by blue lines.
Type I Osteogenesis imperfecta (OI) is a milder form of OI and results from a mutation in the gene for the 1(I) chain which does not produce any protein (deletion or frameshift or nonsense). The result is half as many 1(I) chains and production of only 50% as much collagen. This disorder becomes less severe as the growth rate subsides.
Type II OI is a more severe form of OI and results from a mutation in the gene for the 1(I) chain which alters the amino acid sequence only slightly (missense) but makes the protein incapable of forming a stable, triple helix. Thus, any procollagen molecule containing one mutant chain will be degraded resulting in the production of only 25% of normal amounts of collagen.
This document maintained by Robert J.Huskey
Last update on November 21, 1999.
