Periostin C-Terminal Is Intrinsically Disordered and Interacts with 143 Proteins in an In Vitro Epidermal Model of Atopic Dermatitis

Christian E Rusbjerg-Weberskov, Mette Liere Johansen, Jan Stanislaw Nowak, Daniel Otzen, Jan Skov Pedersen, Jan Johannes Enghild*, Nadia Sukusu Nielsen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Human periostin is a 78–91 kDa matricellular protein implicated in extracellular matrix remodeling, tumor development, metastasis, and inflammatory diseases like atopic dermatitis, psoriasis, and asthma. The protein consists of six domains, including an N-terminal Cys-rich CROPT domain, four fasciclin-1 domains, and a C-terminal domain. The exons encoding the C-terminal domain may be alternatively spliced by shuffling four exons, generating ten variants of unknown function. Here, we investigate the structure and interactome of the full-length variant of the C-terminal domain with no exons spliced out. The structural analysis showed that the C-terminal domain lacked a tertiary structure and was intrinsically disordered. In addition, we show that the motif responsible for heparin-binding is in the conserved very C-terminal part of periostin. Pull-down confirmed three known interaction partners and identified an additional 140 proteins, among which nine previously have been implicated in atopic dermatitis. Based on our findings, we suggest that the C-terminal domain of periostin facilitates interactions between connective tissue components in concert with the four fasciclin domains.
Original languageEnglish
JournalBiochemistry
Volume62
Issue19
Pages (from-to)2803-2815
Number of pages13
ISSN0006-2960
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Cell Adhesion Molecules/genetics
  • Dermatitis, Atopic
  • Exons
  • Humans
  • Intrinsically Disordered Proteins/genetics

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