Sammanfattning

A subset of protein misfolding diseases, including, for example, Alzheimer's disease, is associated with the formation of highly insoluble amyloid fibrils with a beta-sheet structure. The amyloidogenic human lung surfactant protein C (SP-C) is generated from SP-C precursor, which has a C-terminal domain (CTC) that prevents SP-C amyloid fibril formation. Analysis of the substrate specificity of CTC reveals that it binds to all amino acid residues that promote membrane insertion, provided that they are in a nonhelical conformation. In line with this unexpectedly general substrate specificity, the anti-amyloid function of CTC extends to a transmembrane segment other than that of (pro)SP-C, namely, the amyloid beta-peptide associated with Alzheimer's disease. These findings indicate that CTC is the first known chaperone to be directed towards nonhelical transmembrane segments and that it may be employed for the development of new diagnostics or anti-amyloid therapies. (C) 2009 Elsevier Ltd. All rights reserved.

Nyckelord

Brichos domain; chaperone; protein misfolding; membrane protein; amyloid disease

Publicerad i

Journal of Molecular Biology
2009, Volym: 389, nummer: 2, sidor: 227-229
Utgivare: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

SLU författare

• Nerelius, Charlotte

  • Institutionen för anatomi, fysiologi och biokemi, Sveriges lantbruksuniversitet
    

• Nordling, Kerstin

  • Institutionen för anatomi, fysiologi och biokemi, Sveriges lantbruksuniversitet
    

• Johansson, Jan

  • Institutionen för anatomi, fysiologi och biokemi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Biochemistry and Molecular Biology


Publikationens identifierare

DOI: https://doi.org/10.1016/j.jmb.2009.04.021

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/49828