Nordling, Kerstin
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
The C-terminal domain of lung surfactant protein C (CTC) precursor (proSP-C) is involved in folding of the transmembrane segment of proSP-C. CTC includes a Brichos domain with homologs in cancer-and dementia-associated proteins. Mutations in the Brichos domain cause misfolding of proSP-C and hence amyloid fibril formation in interstitial lung disease. Electrospray ionization mass spectrometry (ESI-MS) with collision-induced dissociation (CID) experiments was applied to study non-covalent interactions between human recombinant CTC or its Brichos domain, and SP-C analogs, homotripeptides and peptides designed to model amyloid fibril formation. The results show that the Brichos domain contains the peptide-binding function of CTC. In titration experiments, apparent dissociation constants (K(D)) were in the micromolar range where triple-valine showed the lowest K(D) and triple-tyrosine the highest. Non-hydrophobic peptides failed to form complexes with Brichos. CID revealed that complexes with aromatic peptide ligands are more stable in the gas phase than complexes with non-aromatic ligands. The Brichos domain was also shown to bind fibril-forming peptides containing aromatic/hydrophobic residues. Copyright (C) 2009 John Wiley & Sons, Ltd.
Published in
Rapid Communications in Mass Spectrometry
2009, volume: 23, number: 22, pages: 3591-3598
Publisher: JOHN WILEY & SONS LTD
SLU Authors
Johansson, Jan
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Analytical Chemistry
Publication identifier
- DOI: https://doi.org/10.1002/rcm.4282
Permanent link to this page (URI)
https://res.slu.se/id/publ/49115