Procollagen binds to both prolyl 4-hydroxylase/protein disulfide isomerase and HSP47 within the endoplasmic reticulum in the absence of ascorbate.
In cells, only properly folded procollagen trimers are secreted from the endoplasmic reticulum (ER), while improperly folded abnormal procollagens are retained within the ER. Ascorbic acid is a co-factor in procollagen hydroxylation, which in turn is required for trimer formation. We examined chaperone proteins which bound to procollagen in the absence of ascorbic acid, a model which mimics the human disease scurvy at the cellular level. We found that both prolyl 4-hydroxylase (P4-H)/protein disulfide isomerase (PDI) and HSP47 bound to procollagen in the absence of ascorbic acid. However, the binding of PDI to procollagen decreased when HSP47 was co-transfected, suggesting that HSP47 and PDI compete for binding to procollagen. These data indicate that P4-H/PDI and HSP47 have cooperative but distinct chaperone functions during procollagen biosynthesis.
Hosokawa
N
N
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nagata
K
K
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018832:Molecular Chaperones / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D011817:Rabbits; D014162:Transfection
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011347:Procollagen; C494660:SERPINH1 protein, human; D011393:Procollagen-Proline Dioxygenase; D019704:Protein Disulfide-Isomerases; D001205:Ascorbic Acid