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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\u2019s 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 <jats:italic>Escherichia coli<\/jats:italic> as glutathione-S-transferase or 6\u2009\u00d7\u2009histidine 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\u2019s 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.<\/jats:p>","DOI":"10.1007\/s00726-020-02840-5","type":"journal-article","created":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T01:02:36Z","timestamp":1585270956000},"page":"619-627","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The intracellular domain of BP180\/collagen XVII is intrinsically disordered and partially folds in an anionic membrane lipid-mimicking environment"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7200-6442","authenticated-orcid":false,"given":"Jussi","family":"Tuusa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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