Figure 1
From: EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta
Critical steps in collagen type I biosynthesis and indication of genes known to be involved in OI. Type I collagen is the major structural protein in bone, tendon and ligament. It is first synthesized in the rough endoplasmic reticulum (rER) as type I procollagen, containing C- and N-terminal propeptides. In the rER, the two α1(I)-collagen chains encoded by COL1A1 and the one α2(I)-collagen chain encoded by COL1A2 comprising predominantly Gly-X-Y triplets, align and assemble in the C- to-N direction to form a triple helix. During folding, collagen is modified by, among others, specific enzymes that hydroxylate lysine and proline residues and glycosylate hydroxylysyl residues. This process is called post-translational modification and it stops when triple helix assembly is complete. The CRTAP/P3H1/CyPB complex encoded by the CRTAP, LEPRE1 and PPIB genes, is responsible for the 3-hydroxylation of P986 (p.P1164 counting from the methionine that initiates translation) but will most likely also act as a cis-trans isomerase and a molecular chaperone. FKBP65 encoded by FKBP10 also acts as a molecular chaperone for type I procollagen. The protein product of PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) hydroxylates telopeptide lysines in the rER. HSP47 encoded by SERPINH1 is thought to maintain the stability of the triple helix. After folding, the procollagen molecules are transported through the Golgi apparatus and plasma membrane (PM) into the extracellular matrix (ECM) where cleavage of the N-and C-terminal propeptides occurs and collagen molecules aggregate to form fibrils.
