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

doi:10.1021/acs.biochem.3c00176

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 newspaper › Journal article › Research › peer-review

7 Citations (Scopus)

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 language	English
Journal	Biochemistry
Volume	62
Issue	19
Pages (from-to)	2803-2815
Number of pages	13
ISSN	0006-2960
DOIs	https://doi.org/10.1021/acs.biochem.3c00176
Publication status	Published - Sept 2023

Keywords

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

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10.1021/acs.biochem.3c00176Licence: CC BY-NC-ND

Cite this

@article{ae02f6092260466ab639d781958acee8,

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

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.",

keywords = "Cell Adhesion Molecules/genetics, Dermatitis, Atopic, Exons, Humans, Intrinsically Disordered Proteins/genetics",

author = "Rusbjerg-Weberskov, {Christian E} and Johansen, {Mette Liere} and Nowak, {Jan Stanislaw} and Daniel Otzen and Pedersen, {Jan Skov} and Enghild, {Jan Johannes} and Nielsen, {Nadia Sukusu}",

year = "2023",

month = sep,

doi = "10.1021/acs.biochem.3c00176",

language = "English",

volume = "62",

pages = "2803--2815",

journal = "Biochemistry",

issn = "0006-2960",

publisher = "ACS Publications",

number = "19",

}

Periostin C-Terminal Is Intrinsically Disordered and Interacts with 143 Proteins in an In Vitro Epidermal Model of Atopic Dermatitis. / Rusbjerg-Weberskov, Christian E; Johansen, Mette Liere; Nowak, Jan Stanislaw et al.
In: Biochemistry, Vol. 62, No. 19, 09.2023, p. 2803-2815.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Periostin C-Terminal Is Intrinsically Disordered and Interacts with 143 Proteins in an In Vitro Epidermal Model of Atopic Dermatitis

AU - Rusbjerg-Weberskov, Christian E

AU - Johansen, Mette Liere

AU - Nowak, Jan Stanislaw

AU - Otzen, Daniel

AU - Pedersen, Jan Skov

AU - Enghild, Jan Johannes

AU - Nielsen, Nadia Sukusu

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - Cell Adhesion Molecules/genetics

KW - Dermatitis, Atopic

KW - Exons

KW - Humans

KW - Intrinsically Disordered Proteins/genetics

U2 - 10.1021/acs.biochem.3c00176

DO - 10.1021/acs.biochem.3c00176

M3 - Journal article

C2 - 37704583

SN - 0006-2960

VL - 62

SP - 2803

EP - 2815

JO - Biochemistry

JF - Biochemistry

IS - 19

ER -