2yad

BRICHOS domain of Surfactant protein C precursor protein

spinqualitylabelsall models 2yad, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yad is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PSPC_HUMAN Infant acute respiratory distress syndrome;Interstitial lung disease due to SP-C deficiency;Chronic respiratory distress with surfactant metabolism deficiency;Idiopathic pulmonary fibrosis. The disease is caused by 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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