Structural highlights
Disease
PSPC_HUMAN Interstitial lung disease due to SP-C deficiency;Infant acute respiratory distress syndrome;Chronic respiratory distress with surfactant metabolism deficiency;Idiopathic pulmonary fibrosis. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Function
PSPC_HUMAN Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.
Publication Abstract from PubMed
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 A 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.
High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C.,Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keranen H, Hermansson E, Hamvas A, Nogee LM, Bergman T, Saenz A, Casals C, Aqvist J, Jornvall H, Berglund H, Presto J, Knight SD, Johansson J Proc Natl Acad Sci U S A. 2012 Feb 2. PMID:22308375[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keranen H, Hermansson E, Hamvas A, Nogee LM, Bergman T, Saenz A, Casals C, Aqvist J, Jornvall H, Berglund H, Presto J, Knight SD, Johansson J. High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C. Proc Natl Acad Sci U S A. 2012 Feb 2. PMID:22308375 doi:10.1073/pnas.1114740109
