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J Biol Chem. 2017 Jun 2;292(22):9273-9282. doi: 10.1074/jbc.M116.772657. Epub 2017 Apr 6.

Ziploc-ing the structure 2.0: Endoplasmic reticulum-resident peptidyl prolyl isomerases show different activities toward hydroxyproline.

Author information

1
From the Department of Biochemistry and Molecular Biology, Oregon Health & Science University and.
2
Research Department, Shriners Hospital for Children, Portland, Oregon 97239.
3
From the Department of Biochemistry and Molecular Biology, Oregon Health & Science University and hpb@shcc.org.

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 the cis/trans isomerization of proline peptide bonds is the rate-limiting step during triple-helix formation. Accordingly, the rER-resident peptidyl prolyl cis/trans isomerases (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 PPIases in vitro using 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 the PPIB gene), 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 collagen in vitro and 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.

KEYWORDS:

biosynthesis; collagen; endoplasmic reticulum (ER); molecular chaperone; post-translational modification (PM); prolyl isomerase

PMID:
28385890
PMCID:
PMC5454108
DOI:
10.1074/jbc.M116.772657
[Indexed for MEDLINE]
Free PMC Article

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