title: Ziploc-ing the structure 2.0: Endoplasmic reticulum-resident peptidyl prolyl isomerases show different activities toward hydroxyproline.
abstract: Extracellular matrix proteins are biosynthesized in the rough endoplasmic reticulum (rER), and the triple-helical protein collagen is the most abundant extracellular matrix component in the human body. Many enzymes, molecular chaperones, and post-translational modifiers facilitate collagen biosynthesis. Collagen contains a large number of proline residues, so thecis/transisomerization of proline peptide bonds is the rate-limiting step during triple-helix formation. Accordingly, the rER-resident peptidyl prolylcis/transisomerases (PPIases) play an important role in the zipper-like triple-helix formation in collagen. We previously described this process as "Ziploc-ing the structure" and now provide additional information on the activity of individual rER PPIases. We investigated the substrate preferences of these PPIasesin vitrousing type III collagen, the unhydroxylated quarter fragment of type III collagen, and synthetic peptides as substrates. We observed changes in activity of six rER-resident PPIases, cyclophilin B (encoded by thePPIBgene), FKBP13 (FKBP2), FKBP19 (FKBP11), FKBP22 (FKBP14), FKBP23 (FKBP7), and FKBP65 (FKBP10), due to posttranslational modifications of proline residues in the substrate. Cyclophilin B and FKBP13 exhibited much lower activity toward post-translationally modified substrates. In contrast, FKBP19, FKBP22, and FKBP65 showed increased activity toward hydroxyproline-containing peptide substrates. Moreover, FKBP22 showed a hydroxyproline-dependent effect by increasing the amount of refolded type III collagenin vitroand FKBP19 seems to interact with triple helical type I collagen. Therefore, we propose that hydroxyproline modulates the rate of Ziploc-ing of the triple helix of collagen in the rER.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Oregon Health & Science University and.|Research Department, Shriners Hospital for Children, Portland, Oregon 97239.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Research Department, Shriners Hospital for Children, Portland, Oregon 97239.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Oregon Health & Science University and hpb@shcc.org.|Research Department, Shriners Hospital for Children, Portland, Oregon 97239.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Bächinger
mesh_terms: D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000737:chemistry* / Q000378:metabolism; D021983:Cyclophilins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry / Q000378:metabolism; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C081786:cyclophilin B; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; D006909:Hydroxyproline
keywords: biosynthesis; collagen; endoplasmic reticulum (ER); molecular chaperone; post-translational modification (PM); prolyl isomerase