Interconversion between Serum Amyloid A Native and Fibril Conformations

Yasar F., Sheridan M. S., Hansmann U. H. E.

ACS OMEGA, vol.7, no.14, pp.12186-12192, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 7 Issue: 14
  • Publication Date: 2022
  • Doi Number: 10.1021/acsomega.2c00566
  • Journal Name: ACS OMEGA
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Page Numbers: pp.12186-12192
  • Hacettepe University Affiliated: Yes

Abstract

Overexpression of serum amyloid A (SAA) can lead to a form of amyloidosis where the fibrils are made of SAA fragments, most often SAA(1-76). Using Replica Exchange with Tunneling, we study the conversion of a SAA(1-76) chain between the folded conformation and a fibril conformation. We find that the basins in the free energy landscape corresponding to the two motifs are separated by barriers of only about 2-3 k(B)T. Crucial for the assembly into the fibril structure is the salt bridge 26E-34K that provides a scaffold for forming the fibril conformation.