The Molecular Interactions of Heat Shock Protein 47 (Hsp47) and Their Implications for Collagen Biosynthesis

Abstract

Heat shock protein 47 (Hsp47) is a procollagen/collagen-specific molecular chaperone protein derived from the serpin family of proteins and essential for the early stages of collagen biosynthesis. In this paper, the results of an extensive biophysical analysis of mature recombinant mouse Hsp47 show the existence of both a structurally mesostable monomer with a 5-strand A-sheet and/or a hyperstable trimer; both states have biological activity. It is also demonstrated that Hsp47 is able to bind to a monomeric and partially folded conformation collagen mimic peptide (PPG) 10

Discovery of Novel Tumor Markers of Pancreatic Cancer using Global Gene Expression Technology

“…Genes identified included those involved in cell membrane junctions (claudin 1, connexin 26), 12,13 signal transduction (tumor-associated calcium signal transducer 2, ras GTPase-activating protein-like), 14,15 calcium homeostasis (S100 calcium-binding protein P), 16 cytoskeletal assembly (fascin, keratin 7, rabkinesin6 and pleckstrin), [17][18][19][20] cell surface adhesion and recognition (integrin ␤-like 1), 21 DNA transcription (topoisomerase II␣, transcription factor BMAL2, and AML1), [22][23][24] DNA repair (ATDC), 25 or extracellular matrix remodeling and function (collagens 1␣1, 1␣2, and X1␣1, heat shock protein 47, MMP14, and MMP7). 11,26,27 The cellular localization of the corresponding gene products was also determined using the online database OMIM available through the NCBI web site (http://www.ncbi.nlm.nih.gov/entrez/query). Genes were found to encode membrane-bound proteins (prostate stem cell antigen, OB-cadherin), cytoplasmic proteins (fascin, ATDC), nuclear proteins (topoisomerase II␣, paraneoplastic antigen MA1), as well as extracellular proteins, such as those involved in extracellular matrix homeostasis (hsp47, thrombospondin 2) or secreted protein products (osteopontin).…”

Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells

“…The exact mechanism by which Hsp47 contributes to the production of procollagen is unclear, however. Several possible roles have been proposed including facilitating pro␣ collagen chain elongation, preventing improper association of unassembled and possibly underhydroxylated pro␣ collagen chains (11,13,14), winding of the triple helix (24), maintaining thermal stability of the triple helix once formed (16,25), and diverting assembled procollagen into the cisternal maturation transport pathway (15,26). Although there is experimental support for each of these potential roles, a cohesive model has yet to emerge and not all of the data are consistent.…”

Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site

“…Although PEDF has a putative proteasesensitive loop, unlike classical serpins such as ␣1-antichymotrypsin (ACT), PEDF lacks protease inhibitory activity. Among serpins, this absence of antiprotease activity is not unique to PEDF; heat shock protein 47 (HSP47), a collagen-specific chaperone protein from the serpin family, also lacks antiprotease activity (12). PEDF was originally identified as an extracellular component of the retinal interphotoreceptor matrix (13,14).…”