Cross-strand pairing and amyloid assembly.
Amino acid cross-strand pairing interactions along a beta-sheet surface have been implicated in protein beta-structural assembly and stability, yet the relative contributions have been difficult to evaluate directly. Here we develop the central core sequence of the Abeta peptide associated with Alzheimer's disease, Abeta(16-22), as an experimental system for evaluating these interactions. The peptide allows for internal comparisons between electrostatic and steric interactions within the beta-sheet and an evaluation of these cross-strand pair contributions to beta-sheet registry. A morphological transition from fibers to hollow nanotubes arises from changes in beta-sheet surface complementarity and provides a convenient indicator of the beta-strand strand registry. The intrinsic beta-sequence and pair correlations are critical to regulate secondary assembly. These studies provide evidence for a critical desolvation step that is not present in most models of the nucleation-dependent pathway for amyloid assembly.
Liang
Yan
Y
Center for Fundamental and Applied Molecular Evolution, Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Pingali
Sai Venkatesh
SV
Jogalekar
Ashutosh S
AS
Snyder
James P
JP
Thiyagarajan
Pappannan
P
Lynn
David G
DG