{"entity": "publication", "iuid": "94a5f4debb6349c8bc0051217bd7d8a8", "timestamp": "2026-08-13T00:41:19.178Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/94a5f4debb6349c8bc0051217bd7d8a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/94a5f4debb6349c8bc0051217bd7d8a8"}}, "title": "High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C.", "authors": [{"family": "Willander", "given": "Hanna", "initials": "H"}, {"family": "Askarieh", "given": "Glareh", "initials": "G"}, {"family": "Landreh", "given": "Michael", "initials": "M"}, {"family": "Westermark", "given": "Per", "initials": "P"}, {"family": "Nordling", "given": "Kerstin", "initials": "K"}, {"family": "Ker\u00e4nen", "given": "Henrik", "initials": "H"}, {"family": "Hermansson", "given": "Erik", "initials": "E"}, {"family": "Hamvas", "given": "Aaron", "initials": "A"}, {"family": "Nogee", "given": "Lawrence M", "initials": "LM"}, {"family": "Bergman", "given": "Tomas", "initials": "T"}, {"family": "Saenz", "given": "Alejandra", "initials": "A"}, {"family": "Casals", "given": "Cristina", "initials": "C"}, {"family": "\u00c5qvistg", "given": "Johan", "initials": "J"}, {"family": "J\u00f6rnvall", "given": "Hans", "initials": "H"}, {"family": "Berglund", "given": "Helena", "initials": "H"}, {"family": "Presto", "given": "Jenny", "initials": "J"}, {"family": "Knight", "given": "Stefan D", "initials": "SD"}, {"family": "Johansson", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2012-02-14", "journal": {"volume": "109", "issn": "1091-6490", "issue": "7", "pages": "2325-2329", "title": "Proc. Natl. Acad. Sci. U.S.A.", "issn-l": "0027-8424"}, "abstract": "BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 \u212b crystal structure of the human proSP-C BRICHOS domain, which, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry, reveals how BRICHOS domains may mediate chaperone activity. Observation of amyloid deposits composed of mature SP-C in lung tissue samples from ILD patients with mutations in the BRICHOS domain or in its peptide-binding linker region supports the in vivo relevance of the proposed mechanism. The results indicate that ILD mutations interfering with proSP-C BRICHOS activity cause amyloid disease secondary to intramolecular chaperone malfunction.", "doi": "10.1073/pnas.1114740109", "pmid": "22308375", "labels": {"Protein Science Facility (PSF)": null}, "xrefs": [{"db": "pii", "key": "1114740109"}, {"db": "pmc", "key": "PMC3289314"}, {"db": "PDB", "key": "2YAD"}], "notes": [], "created": "2017-05-04T15:03:45.459Z", "modified": "2017-09-06T11:42:09.198Z"}