The intracellular domain of BP180/collagen XVII is intrinsically disordered and partially folds in an anionic membrane lipid-mimicking environment
| Autor: | M. Kristian Koski, Kaisa Tasanen, Jussi Tuusa, Salla Ruskamo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cytoplasm Protein Folding Clinical Biochemistry Circular dichroism Junctional epidermolysis bullosa (medicine) Autoantigens Biochemistry Cell membrane 03 medical and health sciences 0302 clinical medicine Protein Domains Pemphigoid Bullous Escherichia coli medicine Humans Hemidesmosome Induced folding Protein secondary structure Micelles Hemidesmosome assembly Autoantibodies Basement membrane integumentary system Bullous pemphigoid Chemistry Organic Chemistry Computational Biology Hemidesmosomes Non-Fibrillar Collagens medicine.disease Fusion protein Transmembrane protein 030104 developmental biology medicine.anatomical_structure Biophysics 030217 neurology & neurosurgery |
| Zdroj: | Amino Acids. 52:619-627 |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-020-02840-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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