Molecular modelling assisted design of a TASP mimicking SERPINH1 chaperone function in collagen biosynthesis

SERPINH1 is a 47 kDa heat shock protein belonging to the Serine Protease Inhibitors superfamily, which rather than displaying proteases inhibitor activity, is endowed with a key role in collagen biosynthesis. Unlike other molecular chaperones, hsp47 recognizes selectively the correctly folded state of its client [1], transferring triple helical procollagen molecules from the ER lumen to the Golgi apparatus, thus assisting their folding and preventing improper lateral aggregation [2]. According to hsp47 role as the main collagen superhelix stabilizer, the supportive evidence that its constitutive expression is correlated to major collagen types expression [3], suggests implications in collagenopathies with altered collagen production levels, such as some types of Osteogenesis Imperfecta and Ehlers-Danlos Syndrome. In order to investigate SERPINH1’s actual role in collagen related diseases, we tried to mimic the chaperone moiety of the protein through the design of a Template Assembled Synthetic Protein [4], which should help us in the monitoring of collagen production fluctuations either in normal or in pathological conditions. The resulting new molecules could be considered as the starting point for the further development of novel therapeutic approaches.