2YAD

BRICHOS domain of Surfactant protein C precursor protein

Summary for 2YAD

• Entry DOI: 10.2210/pdb2yad/pdb
• Descriptor: SURFACTANT PROTEIN C BRICHOS DOMAIN (2 entities in total)
• Functional Keywords: pulmonary surfactant system, interstitial lung disease, amyloid, chaperone, surfactant protein
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 6
• Total formula weight: 112253.30

Authors

Askarieh, G.,Siponen, M.I.,Willander, H.,Landreh, M.,Westermark, P.,Nordling, K.,Keranen, H.,Hermansson, E.,Hamvas, A.,Nogee, L.M.,Bergman, T.,Saenz, A.,Casals, C.,Aqvist, J.,Jornvall, H.,Presto, J.,Johansson, J.,Arrowsmith, C.H.,Bountra, C.,Collins, R.,Edwards, A.M.,Ekblad, T.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, I.,Karlberg, T.,Kol, S.,Kotenyova, T.,Kouznetsova, E.,Moche, M.,Nyman, T.,Nordlund, P.,Persson, C.,Schuler, H.,Thorsell, A.G.,Tresaugues, L.,van den Berg, S.,Wahlberg, E.,Weigelt, J.,Welin, M.,Berglund, H.,Knight, S.D. (deposition date: 2011-02-18, release date: 2012-02-15, Last modification date: 2024-10-23)

Primary citation

Willander, H.,Askarieh, G.,Landreh, M.,Westermark, P.,Nordling, K.,Keranen, H.,Hermansson, E.,Hamvas, A.,Nogee, L.M.,Bergman, T.,Saenz, A.,Casals, C.,Aqvist, J.,Jornvall, H.,Berglund, H.,Presto, J.,Knight, S.D.,Johansson, J.
High Resolution Structure of a Bricos Domain and its Implications for Anti-Amyloid Chaperone Activity on Lung Surgactant Protein C.
Proc.Natl.Acad.Sci.USA, 109:2325-, 2012

PubMed 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 Å 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.

PubMed: 22308375
DOI: 10.1073/PNAS.1114740109

Experimental method

X-RAY DIFFRACTION (2.2 Å)