Linked Life Data

48892Evidence393

Source:http://www.reactome.org/biopax/48892Evidence393

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Alignment of the C-terminal prodomains initiates triple helix formation, which propagates in a zipper-like fashion in the C-to-N direction. This occurs in the rough endoplasmic reticulum (Engel & Prockop 1991). Compared with the folding of globular proteins and coiled-coil structures, the concentration-independent folding steps of collagen are extremely slow (Bächinger et al. 1980). Triple helix formation combines a fast process, interpreted as the folding of regions devoid of cis residues, and a slow process, limited by the slow kinetics of cis to trans prolyl-isomerization (Bächinger et al. 1978). Triple-helix formation in regions devoid of cis-prolyl bonds is 3-4 times faster than formation limited by prolyl isomerization reactions (Bachmann et al. 2005). Conversion to trans is required as only trans-peptide bonds can be incorporated into the collagen triple helix (Zeng et al. 1998). Efficient helix folding requires the presence of the 3-prolyl hydroxylation complex. This trimer of Prolyl 3-hydroxylase 1 (LEPRE1), Cyclophilin B (CyPB), also called Peptidyl-prolyl cis-trans isomerase B (PPIB) and CRTAP has 3-prolyl hydroxylase, PPIase and procollagen chaperone properties (Ishikawa et al. 2009, van Dijk et al. 2009). Efficient folding involves additional collagen-specific chaperones such as Serpin H1 (HSP47 - Smith et al. 1995). CyPB belongs to the cyclophilins, a conserved class of intracellular and/or secreted proteins originally identified as cellular binding proteins for the immunosuppressive drug cyclosporin A. They are peptidyl-prolyl cis-trans isomerases (PPIases), which catalyze the cis-trans isomerisation of peptide bonds. CyPB localises to the rough ER but is also secreted extracellularly. It directly interacts with procollagen and is believed to be responsible for converting procollagen cis- to trans-conformers (Zeng et al. 1998). CyPB and Serpin H1 are also involved in procollagen export and secretion. Results obtained with collagen peptides suggest that variations in the Gly-X-Y sequence are likely to result in a non-uniform helical twist along the length of a collagen fibril. Sequences poor in imino acids will have a symmetry close to 10 tripeptide units for every 3 turns of the triple helix (10/3), while stretches of Gly-Pro-Hyp units may have 7/2 symmetry (Brodsky & Persikov 2005).
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