2YAD: Brichos Domain Of Surfactant Protein C Precursor Protein

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.
PDB ID: 2YADDownload
MMDB ID: 97203
PDB Deposition Date: 2011/2/18
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 2YAD: trimeric; determined by author and by software (PISA)
Molecular Components in 2YAD
Label Count Molecule
Proteins (3 molecules)
Surfactant Protein C Brichos Domain
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB