Surface exposed epitopes and structural heterogeneity of in vivo formed transthyretin amyloid fibrils
2006 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 348, no 2, 532-539 p.Article in journal (Refereed) Published
We have investigated the structure of in vivo formed transthyretin (TTR) amyloid deposits by using antisera raised against short linear sequences of the TTR molecule. In immunohistochemistry, antisera anti-TTR41-50 and anti-TTR115-124-a reacted specifically with both wildtype ATTR and ATTR V30M material, whereas only anti-TTR41-50 recognized ATTR Y114C material. Similar results were obtained by ELISA analysis of ATTR V30M and ATTR Y114C vitreous amyloid, where the anti-TTR115-124-a antiserum failed to react with ATTR Y114C material. Moreover, neither of the antisera recognized natively structured TTR present in pancreatic alpha cells. Our results strongly indicate that the TTR molecule undergoes structural changes during fibrillogenesis in vivo. The finding of a structural difference between wildtype ATTR and ATTR V30M material on one hand and ATTR Y114C material on the other suggests that the fibril formation pathway of these ATTR variants may differ in vivo.
Place, publisher, year, edition, pages
2006. Vol. 348, no 2, 532-539 p.
transthyretin, amyloidosis, familial amyloidotic polyneuropathy, fibril, systemic
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-81795DOI: 10.1016/j.bbrc.2006.07.140ISI: 000240275000029PubMedID: 16893521OAI: oai:DiVA.org:uu-81795DiVA: diva2:109710