Anti-Amyloid Activity of the C-Terminal Domain of proSP-C against Amyloid beta-Peptide and Medin
2009 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 48, no 17, 3778-3786 p.Article in journal (Refereed) Published
Amyloid fibrils are found in similar to 25 different diseases, including Alzheimer's disease. Lung surfactant protein C (SP-C) forms fibrils in association with pulmonary disease. It was recently found that the C-terminal domain of proSP-C (CTC), which is localized to the endoplasmic reticulum (ER) lumen, protects the transmembrane (TM) part of (pro)SP-C from aggregation into amyloid until it has a folded into an alpha-helix. CTC appears to have a more general anti-amyloid effect by also acting on TM regions of other proteins. Here we investigate interactions of CTC with the amyloid beta-peptide (A beta) associated with Alzheimer's disease and medin, a peptide that forms fibrils in the most common form of human amyloid. CTC prevents fibril formation in A beta and medin and forms a complex with A beta oligomers, as judged by size-exclusion chromatography and electrospray ionization mass spectrometry. These data suggest that CTC functions as a chaperone that acts preferentially against unfolded TM segments and structural motifs found during amyloid fibril formation, a mechanism that may be exploited in forming a basis for future anti-amyloid therapy.
Place, publisher, year, edition, pages
2009. Vol. 48, no 17, 3778-3786 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-129095DOI: 10.1021/bi900135cISI: 000265528800009PubMedID: 19281242OAI: oai:DiVA.org:uu-129095DiVA: diva2:337570