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Research article - Peer-reviewed, 2006

The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-Val transmembrane segment

Johansson H, Nordling K, Weaver TE, Johansson J


Native lung surfactant protein C (SP-C) is a 4.2-kDa acylpeptide that associates with alveolar surfactant phospholipids via a transmembrane alpha-helix. This helix contains mainly Val, although poly-Val is inefficient in helix formation, and helical SP-C can spontaneously convert to beta-sheet aggregates and amyloid-like fibrils. SP-C is cleaved out from a 21-kDa integral membrane protein, proSP-C, in the alveolar type II cell. Recently several mutations localized in the endoplasmic reticulum-lumenal (C-terminal) part of proSP-C (CTproSP-C) have been associated with intracellular accumulation of toxic forms of proSP-C, low levels of mature SP-C, and development of interstitial lung disease. CTproSP-C contains a similar to 100-residue Brichos domain of unknown function that is also found in other membrane proteins associated with amyloid formation, dementia, and cancer. Here we find that recombinant CTproSP-C binds lipid-associated SP-C, which is in beta-strand conformation, and that this interaction results in an increased helical content. In contrast, CTproSP-C does not bind alpha-helical SP-C. Recombinant CTproSP-C(L188Q), a mutation associated with interstitial lung disease, shows secondary and quaternary structures similar to those of wild type CTproSP-C but is unable to bind lipid-associated beta-strand SP-C. Transfection of CTproSP-C into HEK293 cells that express proSP-C(L188Q) increases the amount of proSP-C protein, whereas no effect is seen on cells expressing wild type proSP-C. These findings suggest that CTproSP-C binds nonhelical SP-C and thereby prevents beta-sheet aggregation and that mutations in CTproSP-C can interfere with this function

Published in

Journal of Biological Chemistry
2006, volume: 281, number: 30, pages: 21032-21039

Authors' information

Willander, Hanna
Swedish University of Agricultural Sciences, Department of Molecular Biosciences
Nordling, Kerstin
Swedish University of Agricultural Sciences, Department of Molecular Biosciences
Johansson, Jan
Swedish University of Agricultural Sciences, Department of Molecular Biosciences
Weaver, TE

UKÄ Subject classification

Veterinary Science
Animal and Dairy Science

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