University of Oulu

Tuusa, J., Koski, M.K., Ruskamo, S. et al. The intracellular domain of BP180/collagen XVII is intrinsically disordered and partially folds in an anionic membrane lipid-mimicking environment. Amino Acids 52, 619–627 (2020).

The intracellular domain of BP180/collagen XVII is intrinsically disordered and partially folds in an anionic membrane lipid-mimicking environment

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Author: Tuusa, Jussi1; Koski, M. Kristian2; Ruskamo, Salla2;
Organizations: 1PEDEGO Research Unit, Department of Dermatology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Springer Nature, 2020
Publish Date: 2020-06-09


The trimeric transmembrane collagen BP180, also known as collagen XVII, is an essential component of hemidesmosomes at the dermal–epidermal junction and connects the cytoplasmic keratin network to the extracellular basement membrane. Dysfunction of BP180 caused by mutations in patients with junctional epidermolysis bullosa or autoantibodies in those with bullous pemphigoid leads to severe skin blistering. The extracellular collagenous domain of BP180 participates in the protein’s triple-helical folding, but the structure and functional importance of the intracellular domain (ICD) of BP180 are largely unknown. In the present study, we purified and characterized human BP180 ICD. When expressed in Escherichia coli as glutathione-S-transferase or 6 × histidine tagged fusion protein, the BP180 ICD was found to exist as a monomer. Analysis of the secondary structure content by circular dichroism spectroscopy revealed that the domain is intrinsically disordered. This finding aligned with that of a bioinformatic analysis, which predicted a disordered structure. Interestingly, both anionic detergent micelles and lipid vesicles induced partial folding of the BP180 ICD, suggesting that in its natural environment, the domain’s folding and unfolding may be regulated by interaction with the cell membrane or accompanying proteins. We hypothesize that the intrinsically disordered structure of the ICD of BP180 contributes to the mechanism that allows the remodeling of hemidesmosome assembly.

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Series: Amino acids
ISSN: 0939-4451
ISSN-E: 1438-2199
ISSN-L: 0939-4451
Volume: 52
Issue: 4
Pages: 619 - 627
DOI: 10.1007/s00726-020-02840-5
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This research was funded by grants from the Sigrid Juselius Foundation to Jussi Tuusa and Kaisa Tasanen, and from the Academy of Finland to Kaisa Tasanen (#294738) and Salla Ruskamo (#275225).
Academy of Finland Grant Number: 294738
Detailed Information: 294738 (Academy of Finland Funding decision)
275225 (Academy of Finland Funding decision)
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